A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.
An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear.
The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
A class of large neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal (not the same as SATELLITE CELLS, PERINEURONAL of GANGLIA) according to their location. They form the insulating MYELIN SHEATH of axons in the central nervous system.
Refers to animals in the period of time just after birth.
A glutamate plasma membrane transporter protein found in ASTROCYTES and in the LIVER.
The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.
A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.
The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.
Aquaporin 4 is the major water-selective channel in the CENTRAL NERVOUS SYSTEM of mammals.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A glial type glutamate plasma membrane transporter protein found predominately in ASTROCYTES. It is also expressed in HEART and SKELETAL MUSCLE and in the PLACENTA.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
A calcium-binding protein that is 92 AA long, contains 2 EF-hand domains, and is concentrated mainly in GLIAL CELLS. Elevation of S100B levels in brain tissue correlates with a role in neurological disorders.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.
A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.
Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
The 2nd cranial nerve which conveys visual information from the RETINA to the brain. The nerve carries the axons of the RETINAL GANGLION CELLS which sort at the OPTIC CHIASM and continue via the OPTIC TRACTS to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the SUPERIOR COLLICULI and the SUPRACHIASMATIC NUCLEI. Though known as the second cranial nerve, it is considered part of the CENTRAL NERVOUS SYSTEM.
A family of POTASSIUM and SODIUM-dependent acidic amino acid transporters that demonstrate a high affinity for GLUTAMIC ACID and ASPARTIC ACID. Several variants of this system are found in neuronal tissue.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.
Neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors. Fibrillary astrocytomas are the most common type and may be classified in order of increasing malignancy (grades I through IV). In the first two decades of life, astrocytomas tend to originate in the cerebellar hemispheres; in adults, they most frequently arise in the cerebrum and frequently undergo malignant transformation. (From Devita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2013-7; Holland et al., Cancer Medicine, 3d ed, p1082)
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of CONNEXINS, the family of proteins which form the junctions.
A 43-kDa peptide which is a member of the connexin family of gap junction proteins. Connexin 43 is a product of a gene in the alpha class of connexin genes (the alpha-1 gene). It was first isolated from mammalian heart, but is widespread in the body including the brain.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A family of highly acidic calcium-binding proteins found in large concentration in the brain and believed to be glial in origin. They are also found in other organs in the body. They have in common the EF-hand motif (EF HAND MOTIFS) found on a number of calcium binding proteins. The name of this family derives from the property of being soluble in a 100% saturated ammonium sulfate solution.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis).
Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.
Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.
An intermediate filament protein found in most differentiating cells, in cells grown in tissue culture, and in certain fully differentiated cells. Its insolubility suggests that it serves a structural function in the cytoplasm. MW 52,000.
The initial culturing of cells derived directly from fresh TISSUES.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.

Astrocyte-specific expression of tyrosine hydroxylase after intracerebral gene transfer induces behavioral recovery in experimental parkinsonism. (1/6371)

Parkinson's disease is a neurodegenerative disorder characterized by the depletion of dopamine in the caudate putamen. Dopamine replacement with levodopa, a precursor of the neurotransmitter, is presently the most common treatment for this disease. However, in an effort to obtain better therapeutic results, tissue or cells that synthesize catecholamines have been grafted into experimental animals and human patients. In this paper, we present a novel technique to express tyrosine hydroxylase (TH) in the host's own astrocytes. This procedure uses a transgene in which the expression of a TH cDNA is under the control of a glial fibrillary acidic protein (GFAP) promoter, which confers astrocyte-specific expression and also increases its activity in response to brain injury. The method was tested in a rat model of Parkinson's disease produced by lesioning the striatum with 6-hydroxydopamine. Following microinjection of the transgene into the denervated striatum as a DNA-liposome complex, expression of the transgene was detected by RT-PCR and TH protein was observed specifically in astrocytes by using double-labeling immunofluorescence for GFAP and TH coupled with laser confocal microscopy. Efficacy was demonstrated by significant behavioral recovery, as assessed by a decrease in the pharmacologically induced turning behavior generated by the unilateral denervation of the rat striatum. These results suggest this is a valuable technique to express molecules of therapeutic interest in the brain.  (+info)

Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. (2/6371)

Nigrostriatal dopaminergic neurons undergo sprouting around the margins of a striatal wound. The mechanism of this periwound sprouting has been unclear. In this study, we have examined the role played by the macrophage and microglial response that follows striatal injury. Macrophages and activated microglia quickly accumulate after injury and reach their greatest numbers in the first week. Subsequently, the number of both cell types declines rapidly in the first month and thereafter more slowly. Macrophage numbers eventually cease to decline, and a sizable group of these cells remains at the wound site and forms a long-term, highly activated resident population. This population of macrophages expresses increasing amounts of glial cell line-derived neurotrophic factor mRNA with time. Brain-derived neurotrophic factor mRNA is also expressed in and around the wound site. Production of this factor is by both activated microglia and, to a lesser extent, macrophages. The production of these potent dopaminergic neurotrophic factors occurs in a similar spatial distribution to sprouting dopaminergic fibers. Moreover, dopamine transporter-positive dopaminergic neurites can be seen growing toward and embracing hemosiderin-filled wound macrophages. The dopaminergic sprouting that accompanies striatal injury thus appears to result from neurotrophic factor secretion by activated macrophages and microglia at the wound site.  (+info)

Early induction of angiogenetic signals in gliomas of GFAP-v-src transgenic mice. (3/6371)

Angiogenesis is a prerequisite for solid tumor growth. Glioblastoma multiforme, the most common malignant brain tumor, is characterized by extensive vascular proliferation. We previously showed that transgenic mice expressing a GFAP-v-src fusion gene in astrocytes develop low-grade astrocytomas that progressively evolve into hypervascularized glioblastomas. Here, we examined whether tumor progression triggers angiogenetic signals. We found abundant transcription of vascular endothelial growth factor (VEGF) in neoplastic astrocytes at surprisingly early stages of tumorigenesis. VEGF and v-src expression patterns were not identical, suggesting that VEGF activation was not only dependent on v-src. Late-stage gliomas showed perinecrotic VEGF up-regulation similarly to human glioblastoma. Expression patterns of the endothelial angiogenic receptors flt-1, flk-1, tie-1, and tie-2 were similar to those described in human gliomas, but flt-1 was expressed also in neoplastic astrocytes, suggesting an autocrine role in tumor growth. In crossbreeding experiments, hemizygous ablation of the tumor suppressor genes Rb and p53 had no significant effect on the expression of VEGF, flt-1, flk-1, tie-1, and tie-2. Therefore, expression of angiogenic signals is an early event during progression of GFAP-v-src tumors and precedes hypervascularization. Given the close similarities in the progression pattern between GFAP-v-src and human gliomas, the present results suggest that these mice may provide a useful tool for antiangiogenic therapy research.  (+info)

Expression of neuropeptide Y receptors mRNA and protein in human brain vessels and cerebromicrovascular cells in culture. (4/6371)

Neuropeptide Y (NPY) has been suggested as an important regulator of CBF. However, except for the presence of Y1 receptors in large cerebral arteries, little is known about its possible sites of action on brain vessels. In this study, we sought to identify the NPY receptors present in the human cerebrovascular bed. Specific Y1 receptor binding sites, localized on the smooth muscle of human pial vessels and potently competed by NPY, polypeptide YY (PYY), and the selective Y1 receptor antagonist BIBP 3226, were identified by quantitative radioautography of the Y1 radioligand [125I]-[Leu31, Pro34]-PYY. In contrast, no specific binding of the Y2-([125I]-PYY3-36) and Y4/Y5-(125I-human pancreatic polypeptide [hPP]) radioligands could be detected. By in situ hybridization, expression of Y1 receptor mRNA was restricted to the smooth muscle layer of pial vessels, whereas no specific signals were detected for either Y2, Y4, or Y5 receptors. Similarly, using reverse transcriptase-polymerase chain reaction (RT-PCR), mRNA for Y1 but not Y2, Y4, or Y5 receptors was consistently detected in isolated human pial vessels, intracortical microvessels, and capillaries. In human brain microvascular cells in culture, PCR products for the Y1 receptors were exclusively found in the smooth muscle cells. In cultures of human brain astrocytes, a cell type that associates intimately with brain microvessels, PCR products for Y1, Y2, and Y4 but not Y5 receptors were identified. Finally, NPY significantly inhibited the forskolin-induced cAMP production in smooth muscle but not in endothelial cell cultures. We conclude that smooth muscle Y1 receptors are the primary if not exclusive NPY receptors associated with human brain extraparenchymal and intraparenchymal blood vessels, where they most likely mediate cerebral vasoconstriction.  (+info)

Translation of the alzheimer amyloid precursor protein mRNA is up-regulated by interleukin-1 through 5'-untranslated region sequences. (5/6371)

The amyloid precursor protein (APP) has been associated with Alzheimer's disease (AD) because APP is processed into the beta-peptide that accumulates in amyloid plaques, and APP gene mutations can cause early onset AD. Inflammation is also associated with AD as exemplified by increased expression of interleukin-1 (IL-1) in microglia in affected areas of the AD brain. Here we demonstrate that IL-1alpha and IL-1beta increase APP synthesis by up to 6-fold in primary human astrocytes and by 15-fold in human astrocytoma cells without changing the steady-state levels of APP mRNA. A 90-nucleotide sequence in the APP gene 5'-untranslated region (5'-UTR) conferred translational regulation by IL-1alpha and IL-1beta to a chloramphenicol acetyltransferase (CAT) reporter gene. Steady-state levels of transfected APP(5'-UTR)/CAT mRNAs were unchanged, whereas both base-line and IL-1-dependent CAT protein synthesis were increased. This APP mRNA translational enhancer maps from +55 to +144 nucleotides from the 5'-cap site and is homologous to related translational control elements in the 5'-UTR of the light and and heavy ferritin genes. Enhanced translation of APP mRNA provides a mechanism by which IL-1 influences the pathogenesis of AD.  (+info)

Micronucleus test using cultured new born rat astrocytes. (6/6371)

Micronuclei is induced in cytoplasm as a consequence of the formation of chromosomal fragments or remaining chromosomes during cell division by the cause of clastogens or spindle poisons, and is used as an indicator of genotoxicity screening tests. There are few short-term genotoxicity screening tests using brain cells. We attempted to establish a new in vitro micronucleus test (MN test) system by use of central nervous system cells. Primary cultured astrocytes were prepared from newborn male Sprague-Dawley (SD) rats. In growth curve of astrocytes, doubling time was determined to be 31 h. In time study, the highest frequency of micronuclei was observed at 48 h, 72 h and 6 h-exposure-66 h-recovery by vincristine (VCR), mitomycin C (MMC) without metabolic activation system and cyclophosphamide (CPM) with metabolic activation system, respectively. Dose-response relationships between micronucleus frequency and concentrations of MMC, VCR and CPM were observed, respectively. It is suggested that the in vitro MN test using new born rat-astrocytes could be used as a screening test of environmental and occupational genotoxic chemicals in the central nervous system cells.  (+info)

Glutamate-, kainate- and NMDA-evoked membrane currents in identified glial cells in rat spinal cord slice. (7/6371)

The effect of L-glutamate, kainate and N-methyl-D-aspartate (NMDA) on membrane currents of astrocytes, oligodendrocytes and their respective precursors was studied in acute spinal cord slices of rats between the ages of postnatal days 5 and 13 using the whole-cell patch-clamp technique. L-glutamate (10(-3) M), kainate (10(-3) M), and NMDA (2x10(-3) M) evoked inward currents in all glial cells. Kainate evoked larger currents in precursors than in astrocytes and oligodendrocytes, while NMDA induced larger currents in astrocytes and oligodendrocytes than in precursors. Kainate-evoked currents were blocked by the AMPA/kainate receptor antagonist CNQX (10(-4) M) and were, with the exception of the precursors, larger in dorsal than in ventral horns, as were NMDA-evoked currents. Currents evoked by NMDA were unaffected by CNQX and, in contrast to those seen in neurones, were not sensitive to Mg2+. In addition, they significantly decreased during development and were present when synaptic transmission was blocked in a Ca2+-free solution. NMDA-evoked currents were not abolished during the block of K+ inward currents in glial cells by Ba2+; thus they are unlikely to be mediated by an increase in extracellular K+ during neuronal activity. We provide evidence that spinal cord glial cells are sensitive to the application of L-glutamate, kainate and transiently, during postnatal development, to NMDA.  (+info)

Carbamazepine-induced upregulation of adenosine A1-receptors in astrocyte cultures affects coupling to the phosphoinositol signaling pathway. (8/6371)

The anticonvulsant and antibipolar drug carbamazepine (CBZ) is known to act as a specific antagonist at adenosine A1-receptors. After a 3-week application of CBZ, A1-receptors are upregulated in the rat brain. We have investigated the consequences of this upregulation for the A1-receptor-mediated signal transduction in primary astrocyte cultures from different regions of the rat brain. CBZ treatment for 10 days had no effect on adenosine A1-receptor mRNA expression in cultures with high basal A1-receptor mRNA levels, but increased A1-receptor mRNA in cultures exhibiting low basal A1-receptor mRNA levels. This upregulation of A1-receptor mRNA was accompanied by an upregulation or induction of A1-receptor-mediated potentiation of PLC activity, a property that was not found in these cultures before CBZ treatment. Thus, CBZ treatment for 10 days induces a new quality of adenosine A1-receptor-mediated signal transduction in cells that express low basal A1-receptor numbers.  (+info)

TY - JOUR. T1 - Acidosis-induced metallothionein (MT) mRNA expression in neonatal rat primary astrocyte cultures. AU - Aschner, M.. AU - Stark, S.. AU - Vrana, K. E.. AU - Conklin, D. R.. PY - 1998/4/15. Y1 - 1998/4/15. N2 - Metallothionein (MT) mRNA levels were determined following exposure of neonatal rat primary astrocyte cultures to acidosis. Astrocyte total RNA was probed on northern blots with [α32P]dCTP-labeled synthetic cDNA probes specific for rat MT isoform mRNAs. The probe for MT-I mRNA hybridized to a single mRNA with a size appropriate for MT, approximately 550 nucleotides. MT-I mRNA levels in astrocyte monolayers exposed to pH 6.5 and 6.0 for 3 or 6 hours were unchanged compared with MT-I mRNA levels in control cultures exposed to pH 7.4. In contrast, 9 hour exposure of astrocytes to pH 6.5 and 6.0 led to a significant increase in MT-I mRNA transcripts compared with controls maintained at pH 7.4 (p,0.001 and p,0.02, respectively). A probe for MT-II mRNA that hybridizes to a single ...
TY - JOUR. T1 - Infection of primary human fetal astrocytes by human herpesvirus 6. AU - Jun, H. E.. AU - McCarthy, Micheline. AU - Zhou, Y. I.. AU - Chandran, Bala. AU - Wood, Charles. PY - 1996/1/29. Y1 - 1996/1/29. N2 - Human herpesvirus 6 (HHV-6) is a lymphotropic betaherpesvirus which productively infects human CD4+ T cells and monocytes. HHV-6 is the etiologic agent for exanthem subitum (roseola), and it is well-known that central nervous system complications occur frequently during the course of HHV-6-associated disease. In addition, HHV-6 has been associated with encephalitis or encephalopathy. However, very little is known about its tropism for neural cells. There are reports that HHV-6 may infect some glial cell lines, but whether it can infect any primary neural cells is not known. Our studies show that both HHV-6A (GS) and HHV-6B (Z-29) can infect highly purified primary fetal astrocytes in vitro. Infected cells showed cytopathic effects, forming giant syncytia. In dual ...
TY - JOUR. T1 - Protein phosphorylation in primary astrocyte cultures treated with and without dibutyryl cyclic AMP. AU - Neary, Joseph T.. AU - Gutierrez, Maria del Pilar. AU - Norenberg, Luz Oliva B.. AU - Norenberg, Michael D.. PY - 1987/4/28. Y1 - 1987/4/28. N2 - Protein phosphorylation was investigated in primary rat astrocyte cultures treated with and without dibutyryl cyclic AMP. Astrocytes maintained in dibutyryl cyclic AMP for several weeks displayed increased phosphate incorporation in 5 protein bands (55, 52, 45, 43 and 28 kDa) while incorporation in one band (42 kDa) was decreased. Phosphate incorporation in several other protein bands was unchanged. Calcium-dependent phosphate incorporation was also altered by prior exposure of the cells to dibutyryl cyclic AMP: addition of calcium to broken cell preparations resulted in increased incorporation in 75, 53 and 52 kDa while decreased incorporation occurred in 100 kDa. These differences in protein phosphorylation may be related to the ...
We report here a novel live imaging approach to study astrocyte response to ischemic injury in the brains of living mice. Our results revealed marked effects of sex and estrogen on astrocyte response to ischemic injury. We report here that: (1) bioluminescent signal intensities/GFAP induction were significantly higher in female mice (out of estrus) compared with males (confirmed by immunohistochemistry); (2) in female mice, astrocyte response to ischemia/GFAP upregulation was strongly dependent on the estrus cycle and serum estrogen level; and (3) contrary to the findings in male mice, there was no correlation between bioluminescent signal intensity/GFAP upregulation and size of the ischemic lesion in female GFAP-luc mice.. GFAP is a 50-kDa intermediate filament, predominantly expressed by mature astrocytes in the central nervous system.24,25 Reactive astrogliosis is a key component of the inflammatory cellular response to central nervous system injury, including ischemia.2,26 It is ...
article{9714ffdf-1e21-475d-ac0b-daebdc2182ca, abstract = {Clearance of the amyloid-P peptide (A beta) as a remedy for Alzheimers disease (AD) is a major target in on-going clinical trials. In vitro studies confirmed that A beta is taken up by rodent astrocytes, but knowledge on human astrocyte-mediated A beta clearance is sparse. Therefore, by means of flow cytometry and confocal laser scanning microscopy (CLSM), we evaluated the binding and internalization of A beta 1-42 by primary human fetal astrocytes and adult astrocytes, isolated from nondemented subjects (n = 8) and AD subjects (n = 6). Furthermore, we analyzed whether alpha 1-antichymotrypsin (ACT), which is found in amyloid plaques and can influence A beta fibrillogenesis, affects the A beta uptake by human astrocytes. Upon over night exposure of astrocytes to FAM-labeled A beta 1-42 (10 mu M) preparations, (80.7 +/- 17.7)% fetal and (52.9 +/- 20.9)% adult A beta-positive astrocytes (P = 0.018) were observed. No significant difference ...
Astrocytes are the major glial subtype in the brain and mediate numerous functions ranging from metabolic support to gliotransmitter release through signaling mechanisms controlled by Ca2+. Despite intense interest, the Ca2+ influx pathways in astrocytes remain obscure, hindering mechanistic insights into how Ca2+ signaling is coupled to downstream astrocyte-mediated effector functions. Here, we identified store-operated Ca2+ release-activated Ca2+ (CRAC) channels encoded by Orai1 and STIM1 as a major route of Ca2+ entry for driving sustained and oscillatory Ca2+ signals in astrocytes after stimulation of metabotropic purinergic and protease-activated receptors. Using synaptopHluorin as an optical reporter, we showed that the opening of astrocyte CRAC channels stimulated vesicular exocytosis to mediate the release of gliotransmitters, including ATP. Furthermore, slice electrophysiological recordings showed that activation of astrocytes by protease-activated receptors stimulated interneurons in ...
Astrocytes derived from Y757F mutant mice defective in gp130-SHP2/SOCS3 signaling were investigated into their ability to respond to IL-6. Compared with WT astrocytes, Y757F astrocytes treated with hyper-IL6, had higher and more sustained activation of STAT3, while the levels of pY-SHP2 and pERK remained unchanged. Gene expression was investigated by Affymetrix gene chip analysis. At 2 hr, 306 genes were upregulated in WT astrocytes and of these, 28 did not increase in Y757F astrocytes. Of 238 genes upregulated in Y757F astrocytes, 9 were not upregulated in WT astrocytes. Some 99 genes were downregulated in WT astrocytes and of those 55 were not decreased in Y757F astrocytes. In WT astrocytes after 12 hrs the level of expression of many genes was reduced back to or near levels seen in the untreated cells, however, in Y757F astrocytes 109 genes either maintained their 2hr upregulated levels or were further increased. A number of candidate genes upregulated by hyper-IL6 in WT and Y757F astrocytes ...
Reactive astrocytes are associated with every form of neurological injury. Despite their ubiquity, the molecular mechanisms controlling their production and diverse functions remain poorly defined. Because many features of astrocyte development are recapitulated in reactive astrocytes, we investigated the role of nuclear factor I-A (NFIA), a key transcriptional regulator of astrocyte development whose contributions to reactive astrocytes remain undefined. Here, we show that NFIA is highly expressed in reactive astrocytes in human neurological injury and identify unique roles across distinct injury states and regions of the CNS. In the spinal cord, after white matter injury (WMI), NFIA-deficient astrocytes exhibit defects in blood-brain barrier remodeling, which are correlated with the suppression of timely remyelination. In the cortex, after ischemic stroke, NFIA is required for the production of reactive astrocytes from the subventricular zone (SVZ). Mechanistically, NFIA directly regulates the ...
Astrocyte activation is presumed to depress neuronal regeneration after CNS injury due to the glial scar, a formation of a physical barrier, and overproduction of multiple proinflammatory cytokines, including IL-1β, IL-6, and TNFα, which further aggravate the glial activation and injure the remaining neurons through positive feedback [4, 31, 38, 39]. The recombinant IL-1β used in the present study was shown to be biologically active as previously demonstrated by its ability to induce astrocyte activation in an in vitro astrocyte activation model [4, 40-42]. Therefore, we speculate that our IL-1β stimulation model is suitable and credible for the detection of the astrocyte activation in vitro. Upregulation of GFAP and hypertrophy of astrocyte cellular processes play a major and prominent role in astrocyte activation and the formation of glial scar [6, 12]. In the present study, the IL-1β stimulation triggered an elevated level of GFAP and induced the astrocyte hypertrophy; this phenomenon ...
The generation of human induced pluripotent stem cells (hiPSCs) represents an exciting advancement with promise for stem cell transplantation therapies as well as for neurological disease modeling. Based on the emerging roles for astrocytes in neurological disorders, we investigated whether hiPSC-derived astrocyte progenitors could be engrafted to the rodent spinal cord and how the characteristics of these cells changed between in vitro culture and after transplantation to the in vivo spinal cord environment. Our results show that human embryonic stem cell- and hiPSC-derived astrocyte progenitors survive long-term after spinal cord engraftment and differentiate to astrocytes in vivo with few cells from other lineages present. Gene profiling of the transplanted cells demonstrates the astrocyte progenitors continue to mature in vivo and upregulate a variety of astrocyte-specific genes. Given this mature astrocyte gene profile, this work highlights hiPSCs as a tool to investigate disease-related ...
TY - JOUR. T1 - Molecular diversity of astrocytes with implications for neurological disorders. AU - Bachoo, Robert M.. AU - Kim, Ryung S.. AU - Ligon, Keith L.. AU - Maher, Elizabeth A.. AU - Brennan, Cameron. AU - Billings, Nathan. AU - Chan, Suzanne. AU - Li, Cheng. AU - Rowitch, David H.. AU - Wong, Wing H.. AU - DePinho, Ronald A.. PY - 2004/6/1. Y1 - 2004/6/1. N2 - The astrocyte represents the most abundant yet least understood cell type of the CNS. Here, we use a stringent experimental strategy to molecularly define the astrocyte lineage by integrating microarray datasets across several in vitro model systems of astrocyte differentiation, primary astrocyte cultures, and various astrocyte-rich CNS structures. The intersection of astrocyte data sets, coupled with the application of nonastrocytic exclusion filters, yielded many astrocyte-specific genes possessing strikingly varied patterns of regional CNS expression. Annotation of these astrocyte-specific genes provides direct molecular ...
Introduction Astrocytes are the most abundant glial cell type. in C57BL/6 mice TNFSF11 astroglial cells in response to lipopolysaccharide (LPS) using reverse-transcription polymerase BMS-911543 BMS-911543 chain reaction (RT-PCR) method. Results We provide for the first time evidence that astrocytes can express IL-19 mRNA following LPS stimulation. Furthermore we have found the expression of IL-19 mRNA in the cortex of adult C57BL/6 mice following intraperitoneal (i.p.) administration of LPS. Discussion This finding will contribute to current knowledge on the function and behavior of cells and mediators during inflammatory conditions in BMS-911543 the brain. Keywords: IL-19 Mice Astroglial Cells brain Cortex Lipopolysaccharide 1 Introduction Glial cells play an important role in controlling of CNS inflammation. Astrocytes are the most abundant glial cell type in the brain (Kim Hong & BMS-911543 Ro 2011 BMS-911543 Astrocytes are multifunctional glial cells that regulate extracellular ion and ...
In the present study, we aim to elucidate the role of caveolin-1 in modulating astroglial differentiation of neural progenitor cells (NPCs) and the potential mechanisms involved. We first investigated astroglial differentiation and Notch signaling by detecting the expressions of S100β, GFAP, NICD and hairy enhancer of split 1 (Hes1) in the brains of wild-type and caveolin-1 knockout mice. Caveolin-1 knockout mice revealed remarkably less astroglial differentiation and lower levels of NICD and Hes1 expressions than wild type mice. We then studied the potential roles of caveolin-1 in modulating NICD and Hes1 expressions and astroglial differentiation in isolated cultured NPCs by using caveolin-1 peptide and caveolin-1 RNA silencing. In the differentiating NPCs, caveolin-1 peptide markedly promoted astroglial formation and up-regulated the expressions of NICD and Hes1. In contrast, the knockdown of caveolin-1 inhibited astroglial differentiation of NPCs and the expressions of NICD and Hes1. Taken ...
Antigen presentation reactions are dependent upon the expression of the class II major histocompatibility antigens (MHC), the T-cell receptor, and the presented antigen. Recent studies demonstrate that such processes also require the presence of adhesion molecules such as lymphocyte functional antigen 1 (LFA-1) and its cell surface ligand, intercellular adhesion molecule 1 (ICAM-1). It has been suggested that the brain astrocyte can function as a facultative antigen presenting cell (APC). This hypothesis is based upon the ability to induce the expression of the class II MHC antigens on astrocytes, and on their ability to present myelin basic protein to encephalitogenic T-cells in vitro. The best in vivo data showing that astrocytes serve as intracerebral APCs is the finding that astrocytes in multiple sclerosis plaques are DR+ (class II MHC in human). However, it still remains to be resolved whether the in vivo expression of the MHC antigens in disease states is instrumental to antigen presentation
TY - JOUR. T1 - Induction of Alzheimer-specific tau epitope AT100 in apoptotic human fetal astrocytes. AU - Ksiezak-Reding, Hanna. AU - He, Deke. AU - Gordon-Krajcer, Wanda. AU - Kress, Yvonne. AU - Lee, Sunhee. AU - Dickson, Dennis W.. PY - 2000. Y1 - 2000. N2 - In Alzheimers and other neurodegenerative diseases, hyperphosphorylated tau accumulates in affected neuronal and glial cells in the form of paired helical filaments (PHFs). This tau binds antibody AT100, which recognizes the double phosphorylation site (Thr212/Ser214) that is not present in normal biopsy tau. In primary cultures, highly enriched (,98%) in astrocytes of human fetal brain, three polypeptides of 52, 64, and 70 kD showed immunoreactivity with tau antibodies against non-phosphorylated epitopes, accounting for 88, 12, and ,1%, respectively, of the total reactivity. All three polypeptides were phosphorylated at the PHF-1 epitope but not at the epitopes Tau-1, 12E8, AT8, and AT100. Treatment of cultures with okadaic acid ...
TY - JOUR. T1 - Synergistic induction of astrocytic differentiation by factors secreted from meninges in the mouse developing brain. AU - Kawamura, Yoichiro. AU - Katada, Sayako. AU - Noguchi, Hirofumi. AU - Yamamoto, Hiroyuki. AU - Sanosaka, Tsukasa. AU - Iihara, Koji. AU - Nakashima, Kinichi. PY - 2017/11. Y1 - 2017/11. N2 - Astrocytes, which support diverse neuronal functions, are generated from multipotent neural stem/precursor cells (NS/PCs) during brain development. Although many astrocyte-inducing factors have been identified and studied in vitro, the regions and/or cells that produce these factors in the developing brain remain elusive. Here, we show that meninges-produced factors induce astrocytic differentiation of NS/PCs. Consistent with the timing when astrocytic differentiation of NS/PCs increases, expression of astrocyte-inducing factors is upregulated. Meningeal secretion-mimicking combinatorial treatment of NS/PCs with bone morphogenetic protein 4, retinoic acid and leukemia ...
In this study, we focused on four glial proteins that are abundant in amyloid plaques and/or that are known to interact with Abeta: alpha1-antichymotrypsin (ACT), interleukin-1beta (IL-1beta), S100beta, and butyrylcholinesterase (BChE). We examined the ability of these proteins to activate rat cortical astrocyte cultures and to influence the ability of Abeta to activate astrocytes. Treatment of astrocytes with ACT, IL-1beta, or S100beta resulted in glial activation, as assessed by reactive morphology, upregulation of IL-1beta, and production of inducible nitric oxide synthase and nitric oxide. The ability of Abeta to induce astrocyte activation was also enhanced in the presence of each of these three proteins. In contrast, BChE alone did not activate astrocytes and had no effect on Abeta-induced activation ...
Astrocytes, which constitute 40% to 70% of total cells in the CNS [1], perform key regulatory functions critical to brain function. The different CNS cell types are differentially infected with HIV; microglia being highly susceptible, astrocytes moderately restrictive, and neurons highly restrictive. Despite the lack of CD4 receptors, astrocytes become infected via CD4-independent mechanism [6,44]. In line with the earlier studies [1,2], we also found low level of HIV replication in astrocytes compared to microglia. After the initial productive phase, infection subsides to a persistent stage in astrocytes, which goes in hand with reports from other investigators [1,2,32]. Infected astrocytes produce very low levels of virus even in the acute phase in contrast to infection of T-lymphocytes [45,46]. Our results with pseudotyped virus confirm that regardless of the entry routes, there are post-entry blocks to infection in astrocytes. Though the introduction of potent HAART has significantly ...
OASIS is a member of the CREB/ATF family of transcription factors and modulates cell- or tissue-specific unfolded protein response signalling. Here we show that this modulation has a critical role in the differentiation of neural precursor cells into astrocytes. Cerebral cortices of mice specifically deficient in OASIS (Oasis−/−) contain fewer astrocytes and more neural precursor cells than those of wild-type mice during embryonic development. Furthermore, astrocyte differentiation is delayed in primary cultured Oasis−/− neural precursor cells. The transcription factor Gcm1, which is necessary for astrocyte differentiation in Drosophila, is revealed to be a target of OASIS. Introduction of Gcm1 into Oasis−/− neural precursor cells improves the delayed differentiation of neural precursor cells into astrocytes by accelerating demethylation of the Gfap promoter. Gcm1 expression is temporally controlled by the unfolded protein response through interactions between OASIS family members ...
We have used digital fluorescence imaging techniques to explore the interplay between mitochondrial Ca2+ uptake and physiological Ca2+ signaling in rat cortical astrocytes. A rise in cytosolic Ca2+ ([Ca2+]cyt), resulting from mobilization of ER Ca2+ stores was followed by a rise in mitochondrial Ca2+ ([Ca2+]m, monitored using rhod-2). Whereas [Ca2+]cyt recovered within ~1 min, the time to recovery for [Ca2+]m was ~30 min. Dissipating the mitochondrial membrane potential ( Dcm, using the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxy-phenylhydrazone [FCCP] with oligomycin) prevented mitochondrial Ca2+ uptake and slowed the rate of decay of [Ca2+]cyt transients, suggesting that mitochondrial Ca2+ uptake plays a significant role in the clearance of physiological [Ca2+]cyt loads in astrocytes. Ca2+ signals in these cells initiated either by receptor-mediated ER Ca2+ release or mechanical stimulation often consisted of propagating waves (measured using fluo-3). In response to either ...
When DArcy Wentworth Thompsons On Growth and Form was published 100 years ago, it raised the question of how biological forms arise during development and across evolution. In light of the advances in molecular and cellular biology since then, a succinct modern view of the question states: how do genes encode geometry? Our new special issue is packed with articles that use mathematical and physical approaches to gain insights into cell and tissue patterning, morphogenesis and dynamics, and that provide a physical framework to capture these processes operating across scales.. Read the Editorial by guest editors Thomas Lecuit and L. Mahadevan, as they provide a perspective on the influence of DArcy Thompsons work and an overview of the articles in this issue.. ...
In the astrocyte lineage, Meteorin expression appears to be restricted to relatively immature cell populations. Meteorin expression is gradually lost in GLAST‐expressing astrocytes located in the postnatal cerebral parenchyma (Figure 2K and L), and is not detected in two major types of astrocytes in the adult cerebrum, fibrous astrocytes and protoplasmic astrocytes (Miller and Raff, 1984) (Supplementary Figure 3G). In the developing cerebellum, Meteorin is expressed in the VZ and GLAST‐positive migrating glial precursors. Among three subclasses of astrocytes in the adult cerebellar cortex, bushy protoplasmic astrocytes, smooth protoplasmic astrocytes, and Bergmann glia (Palay and Chan‐Palay, 1974), Meteorin expression is restricted to Bergmann glia (Figure 2M and N) (Supplementary Figure 3H and I). Expression of Meteorin in Bergmann glia may be regulated by neurons that interact with Bergmann glia. For instance, dendritic spines of Purkinje cells were completely enwrapped by Bergmann glial ...
The cells we identify here as primary precursors for new neurons in the adult hippocampus have the characteristics of astrocytes at the light and electron microscope. They contain multiple processes with intermediate filaments rich in GFAP. Results from three independent experiments support this conclusion. First, many proliferating SGL astrocytes rapidly convert to a cell type that is GFAP negative and that possesses characteristics of D cells. Second, anti-mitotic treatment resulted in the elimination of D cells from the SGL, but neurogenesis returned. Because new neurons are born at a time when [3H]thymidine-labeled astrocytes were observed, we infer that astrocytes function as primary precursors. Finally, we show that SGL astrocytes, specifically labeled with an avian retrovirus, give rise to granule neurons. We observed granule neurons at different stages of maturation by killing animals at different survivals after retroviral infection. Some SGL astrocytes remain labeled with thymidine ...
Tenascin-C is an extracellular matrix glycoprotein with trophic and repulsive properties on neuronal cells, involved in migratory processes of immature neurons. Previous reports demonstrated that this molecule is produced and secreted by astrocytes, in vitro after activation by bFGF or in vivo after CNS lesion. In injured brain the expression of tenascin-C has been correlated with the glial reaction since it was observed in regions suffering a dramatic glial proliferation and hypertrophy. In this report we show that the treatment of cultured hippocampal astrocytes with tenascin-C results in an increased fibronectin and NCAM immunoreactivities. In addition, treated astrocytes form longer extensions than control ones. The number of cells as well as the levels of GFAP mRNA and protein immunoreactivity are not modified after tenascin-C treatment. The present changes may, therefore, be related to the modification of the adhesive properties of astrocytes to the substrate. These observations are compatible
Repairing trauma to the central nervous system by replacement of glial support cells is an increasingly attractive therapeutic strategy. We have focused on the less-studied replacement of astrocytes, the major support cell in the central nervous system, by generating astrocytes from embryonic human glial precursor cells using two different astrocyte differentiation inducing factors. The resulting astrocytes differed in expression of multiple proteins thought to either promote or inhibit central nervous system homeostasis and regeneration. When transplanted into acute transection injuries of the adult rat spinal cord, astrocytes generated by exposing human glial precursor cells to bone morphogenetic protein promoted significant recovery of volitional foot placement, axonal growth and notably robust increases in neuronal survival in multiple spinal cord laminae. In marked contrast, human glial precursor cells and astrocytes generated from these cells by exposure to ciliary neurotrophic factor both failed
One barrier to studying astrocytes has been the difficulty of isolating and culturing the mature cell from the brain. Most current protocols isolate precursor cells rather than mature astrocytes. These precursor cells proliferate in culture in the presence of serum, developing a flat, fibroblast-like appearance that bears little resemblance to astrocytes in the brain (see image above). Other isolation methods, such as fluorescence-activated cell sorting, are too harsh to produce viable cells, co-first author Ye Zhang told Alzforum.. To gently isolate mature astrocytes for culturing, Zhang and co-first author Steven Sloan developed an immunopanning protocol. In this procedure, dissociated cells from brain tissue were passed through several culture dishes coated with antibodies to specific cell-surface markers. The first several plates removed unwanted cell types, while the final plate contained anti-HepaCAM to capture astrocytes. After washing off contaminating cells, the authors detached the ...
The 14-3-3 protein family plays critical regulatory roles in signaling pathways in cell division and apoptosis. 14-3-3gamma is mainly expressed in brain. Using primary cultures of cerebral cortical astrocytes, we investigated the relationships between 14-3-3gamma proteins and actin in astrocytes in cell division and under ischemia. Our results showed that endogenous 14-3-3gamma proteins in immature astrocytes appeared filamentous and co-localized with filamentous actin (F-actin). During certain stages of mitosis, 14-3-3gamma proteins first aggregated and then formed a ring-like structure that surrounded the daughter nuclei and enclosed the F-actin. In 4-week-old cultures of astrocytes, 14-3-3gamma proteins appeared as punctate aggregates in the cytoplasm. Under ischemia, 14-3-3gamma proteins formed filamentous structures and were closely associated with F-actin in surviving astrocytes. However, in apoptotic astrocytes, the intensity of immunostaining of 14-3-3gamma proteins in the cytoplasm ...
In cell migration assays, spheroids are seeded on an astrocyte monolayer culture, so the glioma cells do not penetrate the astrocyte culture and the migration is two-dimensional. This is the reason why we considered two layers in the model: one layer is the astrocyte on top of which lies the tumour cell layer. Thus, glioma cells and astrocytes can occupy the same position but on different planes. For all practical purposes, astrocytes in a confluent monolayer culture could be considered as non-motile cells. Time-lapse experiments registered only chaotic non-directional movements of negligible magnitude 1.24±0.36 μm in 5 h.. The rules of motion inside the layer of glioma cells are exactly the same as described before, for migration on a passive substrate: in the control situation we have p+=1, whereas in the treated situation we take p−=0.5. For the sake of coherency, we model the heterotype GJ communication as we did for homotype communication, i.e. with a parameter q which quantifies the ...
Functionally diversified neuronal populations have been efficiently generated from human pluripotent stem cells (hPSCs). rostral-caudal and dorsal-ventral identities with the same morphogens used for neuronal subtype specification generate immature astrocytes that carry distinct homeodomain transcription factors and display phenotypic differences. These human astroglial progenitors and immature astrocytes will be instrumental for studying astrocytes in brain development and function for revealing their roles in disease processes and for developing novel treatments for neurological disorders. INTRODUCTION Astroglial cells are the most abundant cell type in our brain and spinal cord and are now understood to be as important as neurons for brain function1 2 During development astroglial progenitors are specified after neurogenesis even though the identity of the progenitors isnt well described due to R935788 insufficient dependable markers3 4 These progenitors differentiate to immature astrocytes ...
We found that cultured mouse cortical astrocytes display circadian rhythms in extracellular ATP, in agreement with recent results from rat astrocyte cultures, SCN and SCN2.2 cells (Womac et al., 2009). We used a stabilized form of luciferase that allowed long-term recordings of extracellular ATP from the same cells without perturbations that can affect circadian clock-gene expression in astrocytes (Prolo et al., 2005). We found that Clock/Clock, Per1m Per2m, Cry1−/−Cry2−/− and Bmal1−/− astrocytes are arrhythmic, similar to the locomotor behavior deficits of these mice (Vitaterna et al., 1994; van der Horst et al., 1999; Bunger et al., 2000; Zheng et al., 2001). We found that Bmal1, Clock−/+ and Cry1−/−Cry2−/+ glia have abnormal periods, much like the heterozygous mouse behavior. The correlations between rhythmicity in clock genes, extracellular ATP in glia and locomotor behavior suggest they may be tightly related.. Most of the astrocyte cultures deficient for functional ...
The central finding of the present study is that Mt3 plays a key role in the clathrin-dependent endocytosis of Aβ in astrocytes. In Mt3 −/− astrocytes, clathrin-mediated endocytosis, the mechanism responsible for Aβ endocytosis, was markedly decreased, whereas caveolin-mediated endocytosis was not altered. Astrocytes are likely key players in the clearance of extracellular Aβ; thus, our results suggest that changes in the Mt3 expression in astrocytes may have clinical relevance in AD. Taken together with our previous findings that Mt3 helps to maintain lysosomal degradation in astrocytes, the reduction in Mt3 in astrocytes may aggravate Aβ accumulation in the extracellular space.. Early studies showed that AD brain extracts induce more neurite outgrowth in cell cultures than do control brain extracts [27], suggesting upregulation of a growth-inducing factor or downregulation of a growth-inhibitory factor (GIF) in AD brains. The latter was shown to be the case, and a subsequent study ...
To better characterize the electrophysiological properties of neonatal astrocytes, we purposely narrowed the animal age to the dormant P1-3 period for examining potential diversity in ion channel expression among neonatal astrocytes. Interestingly, two electrophysiological phenotypes could be readily identified during this early postnatal age. The neonatal astrocytes in P1 homogeneously show a variably rectifying whole cell current profile, whereas electrophysiologically passive astrocytes (PAs) first appear in P2, and the percentage of PAs rapidly increased from 6.67 % in P2 to 20.83 % at P3. Interestingly, the appearance of PA in mice is 2 days earlier than rats [2], which seemingly follows a longer gestation time in rats (22 day) than mice (20 day).. We show that the passive behavior of neonatal astrocytes is solely attributable to gap junction coupling (Fig. 3). This differs fundamentally from the passive behavior of membrane conductance in mature astrocytes that is caused by intrinsic K+ ...
Neurogenesis is restricted in the adult mammalian brain; most neurons are neither exchanged during normal life nor replaced in pathological situations. We report that stroke elicits a latent neurogenic program in striatal astrocytes in mice. Notch1 signaling is reduced in astrocytes after stroke, and attenuated Notch1 signaling is necessary for neurogenesis by striatal astrocytes. Blocking Notch signaling triggers astrocytes in the striatum and the medial cortex to enter a neurogenic program, even in the absence of stroke, resulting in 850 ± 210 (mean ± SEM) new neurons in a mouse striatum. Thus, under Notch signaling regulation, astrocytes in the adult mouse brain parenchyma carry a latent neurogenic program that may potentially be useful for neuronal replacement strategies. ...
Astrocytes are now recognized as dynamic signaling elements in the brain. Bidirectional communication between neurons and astrocytes involves integration of neuronal inputs by astrocytes and release of gliotransmitters that modulate neuronal excitability and synaptic transmission. The ovarian steroid hormone, 17\beta-estradiol, in addition to its rapid actions on neuronal electrical activity can rapidly alter astrocyte intracellular calcium concentration $([Ca^{2+}]_i)$ through a membrane-associated estrogen receptor. Using calcium imaging and electrophysiological techniques, we investigated the functional consequences of acute treatment with estradiol on astrocyte-astrocyte and astrocyte-neuron communication in mixed hippocampal cultures. Mechanical stimulation of an astrocyte evoked a $[Ca^{2+}]_i$ rise in the stimulated astrocyte, which propagated to the surrounding astrocytes as a $[Ca^{2+}]_i$ wave. Following acute treatment with estradiol, the amplitude of the $([Ca^{2+}]_i)$ elevation in ...
Astrocytes are the most abundant and functionally diverse glial population in the vertebrate central nervous system (CNS). However, the mechanisms underlying astrocyte specification are poorly understood. It is well established that cellular diversification of neurons in the embryo is generated by position-dependent extrinsic signals and combinatorial interactions of transcription factors that direct specific cell fates by suppressing alternative fates. It is unknown whether a comparable process determines embryonic astrocyte identity. Indeed, astrocyte development is generally thought to take place in a position-independent manner. Here we show multiple functions of Stem cell leukaemia (Scl, also known as Tal1), which encodes a basic helix-loop-helix (bHLH) transcription factor, in the regulation of both astrocyte versus oligodendrocyte cell fate acquisition and V2b versus V2a interneuron cell fate acquisition in the p2 domain of the developing vertebrate spinal cord. Our findings demonstrate a
Aquaporin-4 (AQP4) is the predominant water channel in brain and is selectively expressed in astrocytes. Astrocytic endfoot membranes exhibit tenfold higher densities of AQP4 than non-endfoot membranes, making AQP4 an excellent marker of astrocyte polarization. Loss of astrocyte polarization is known to compromise astrocytic function and to be associated with impaired water and K+ homeostasis. Here we investigate by a combination of light and electron microscopic immunocytochemistry whether amyloid deposition is associated with a loss of astrocyte polarization, using AQP4 as a marker. We used the tg-ArcSwe mouse model of Alzheimers disease, as this model displays perivascular plaques as well as plaques confined to the neuropil. 3D reconstructions were done to establish the spatial relation between plaques and astrocytic endfeet, the latter known to contain the perivascular pool of AQP4. Changes in AQP4 expression emerge just after the appearance of the first plaques. Typically, there is a loss ...
This cellular imaging study in animal models will explore whether two genetically determined forms of autism spectrum disorder (ASD) have similar deleterious alterations in star-shaped cells, called astrocytes, that adversely affect brain development. Two genetic forms of ASD are Retts syndrome, which occurs almost exclusively in girls, and Fragile X syndrome, which occurs predominately in boys. Prior research showed that defects occur in neurons. More recent research indicates that defects occur as well in other types of cells in the brain, including astrocytes. While there are billions of nerve cells in the brain, there are even more astrocytes. Research suggests that astrocytes can produce both advantageous and deleterious effects. In the developing brain, astrocytes have a key role in regulating nerve cells functions. If astrocytes are altered, however, they may adversely affect brain development. The investigators hypothesize that both in Retts syndrome and Fragile X syndrome, as well ...
There is now growing evidence that astrocytes, like neurons, can release transmitters. One transmitter that in a vast number of studies has been shown to be released from astrocytes is glutamate. Although asytrocytic glutamate may be released by several mechanisms, the evidence in favor of exocytosis is most compelling. Astrocytes may respond to neuronal activity by such exocytotic release of glutamate. The astrocyte derived glutamate can in turn activate neuronal glutamate receptors, in particular N-methyl-D-aspartate (NMDA) receptors. Here we review the morphological data supporting that astrocytes possess the machinery for exocytosis of glutamate. We describe the presence of small synaptic-like microvesicles, SNARE proteins and vesicular glutamate transporters in astrocytes, as well as NMDA receptors situated in vicinity of the astrocytic vesicles.
The pathophysiology of a traumatic brain injury (TBI) involves the dysfunction of the blood-brain barrier (BBB). The lumen of the BBB is lined with cerebrovascular endothelial cells (CVEC) that are ensheathed with perivascular astrocyte endfeet. We investigated the cellular response of human-astrocytes and human-CVEC following trauma in vitro. Astrocytes and CVEC were subjected to a concussive injury (CI; mechanical stretch), then assessed for markers of injury (monolayer retraction) and activation (mitogen-activated protein kinases (MAPK) phosphorylation). CI induces astrocyte monolayer retraction and activation, with predominant phosphorylation of JNK1/2 MAPK. Interfering with JNK1/2 activation (selective JNK inhibitors) reduces trauma-induced astrocyte retraction. On the contrary, CI does not induce CVEC retraction, however up-regulates CVEC pro-adhesive phenotype resulting in increased polymorphonuclear leukocyte (PMN) adhesion. These findings indicate that CI elicits differential BBB cell responses
We used the pH-sensitive fluorescent dye BCECF to study intracellular pH (pHi) regulation in primary cultures of rat astrocytes and C6 glioma cells. Both cell types contain three pH-regulating transporters: (1) alkalinizing Na+/H+ exchange; (2) alkalinizing Na+ + HCO3 −/Cl−exchange; and (3) acidifying Cl−/HCO3− exchange. Na+/H+ exchange was most evident in the absence of CO2; recovery from acidification was Na+ dependent and amiloride sensitive. Exposure to CO2 caused a cell alkalinization that was inhibited by DIDS, dependent on external Na+, and inhibited 75% in the absence of Cl− (thus mediated by Na+ + HCO3−/Cl− exchange). When pHi was increased above the normal steady-state pHi, a DIDS-inhibitable and Na+ -independent acidifying recovery was evident, indicating the presence of Cl− /HCO3−exchange. Astrocytes, but not C6 cells, contain a fourth pH-regulating transporter, Na+ −HCO3− cotransport; in the presence of CO2, depolarization caused an alkalinization of 0.12 +− 0.01 (n
Blood-brain barrier (BBB) function is regulated by dynamic interactions among cell types within the neurovascular unit, including astrocytes and endothelial cells. Co-culture models of the BBB typically involve astrocytes seeded on two-dimensional (2D) surfaces, which recent studies indicate cause astrocytes to express a phenotype similar to that of reactive astrocytes in situ. We hypothesized that the culture conditions of astrocytes would differentially affect their ability to modulate BBB function in vitro. Brain endothelial cells were grown alone or in co-culture with astrocytes.
Huntingtons Disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion, resulting in a mutant huntingtin protein. While it is now clear that astrocytes are affected by HD and significantly contribute to neuronal dysfunction and pathogenesis, the alterations in the transcriptional and epigenetic profiles in HD astrocytes have yet to be characterized. Here, we examine global transcription and chromatin accessibility dynamics during in vitro astrocyte differentiation in a transgenic non-human primate model of HD. We found global changes in accessibility and transcription across different stages of HD pluripotent stem cell differentiation, with distinct trends first observed in neural progenitor cells (NPCs), once cells have committed to a neural lineage. Transcription of p53 signaling and cell cycle pathway genes was highly impacted during differentiation, with depletion in HD NPCs and upregulation in HD astrocytes. E2F target genes also displayed this inverse expression pattern,
In this study, we investigated the role of the Arp2/3 complex and associated signaling in astrocytes. We demonstrate that the expansion of astrocytic cell bodies and processes is triggered by Arp2/3 inhibition in dissociated cultures and brain tissue. This phenomenon requires the activity of myosin II in conjunction with increased RhoA activity. Furthermore, we identified N-WASP and PICK1 as crucial Arp2/3 regulators in astrocyte morphological plasticity, and show that this mechanism underlies the rapid and drastic morphological changes exhibited by astrocytes under ischemic conditions.. In most studied cell types, inactivation of the Arp2/3 complex leads mainly to disappearance, outgrowth-inhibition or shrinkage of subcellular structures such as lamellipodia in fibroblasts and cancer cells (Steffen et al., 2006; Wu et al., 2012), or neurites and dendritic spines in neurons (Korobova and Svitkina, 2008; Hotulainen et al., 2009; Tahirovic et al., 2010; Nakamura et al., 2011; Yang et al., 2012). ...
Glutamate transporters (GluTs) maintain a low ambient level of glutamate in the central nervous system (CNS) and shape the activation of glutamate receptors at synapses. Nevertheless, the mechanisms that regulate the trafficking and localization of transporters near sites of glutamate release are poorly understood. Here, we examined the subcellular distribution and dynamic remodeling of the predominant GluT GLT-1 (excitatory amino acid transporter 2, EAAT2) in developing hippocampal astrocytes. Immunolabeling revealed that endogenous GLT-1 is concentrated into discrete clusters along branches of developing astrocytes that were apposed preferentially to synapsin-1 positive synapses. Green fluorescent protein (GFP)-GLT-1 fusion proteins expressed in astrocytes also formed distinct clusters that lined the edges of astrocyte processes, as well as the tips of filopodia and spine-like structures. Time-lapse three-dimensional confocal imaging in tissue slices revealed that GFP-GLT-1 clusters were ...
Despite successful management of ruptured intracranial aneurysm following subarachnoid hemorrhage (SAH), delayed cerebral ischemia (DCI) remains the main cause of high mortality and morbidity in patients who survive the initial bleeding. Astrocytes play a key role in neurovascular coupling. Therefore, changes in the neurovascular unit including astrocytes following SAH may contribute to the development of DCI and long-term complications. In this study, we characterized morphological changes in hippocampal astrocytes following experimental SAH, with special emphasis on glia-vascular cross-talk and hippocampal volume changes. Four days after induction of SAH or sham-operation in mice, their hippocampal volumes were determined by magnetic resonance imaging (MRI) and histological/stereological methods. Glial fibrillary acid protein (GFAP) immunostained hippocampal sections were examined by stereological techniques to detect differences in astrocyte morphology, and global spatial sampling method was ...
TY - JOUR. T1 - The protective effects of coumestrol against amyloid-beta peptide- and lipopolysaccharide-induced toxicity on mice astrocytes. AU - Liu, Man Hai. AU - Tsuang, Fon Yih. AU - Sheu, Shiow Yunn. AU - Sun, Jui Sheng. AU - Shih, Chi Ming. PY - 2011/7. Y1 - 2011/7. N2 - Objectives: Estrogen replacement therapy can decrease the risk of developing Alzheimers disease. Phytoestrogens have been proposed as potential alternatives to estrogen replacement therapy. The purpose of this study was to evaluate the in vitro protective effects of coumestrol on mice astrocytes. Methods: Different concentrations of coumestrol were tested for their protective efficacy against two toxic insults, lipopolysaccharide (LPS) and amyloid-beta peptide, on astrocytes. The mitochondrial activity of astrocytes was determined, and the protective efficacy and pathway were examined by their specific gene expression and protein change. Results: The results showed that coumestrol induced a modest but significant ...
Astrocyte activation is a characteristic response to injury in the central nervous system, and can be either neurotoxic or neuroprotective, while the regulation of both roles remains elusive. To decipher the regulatory elements controlling astrocyte-mediated neurotoxicity in glaucoma, we conducted a systems-level functional analysis of gene expression, proteomic and genetic data associated with reactive optic nerve head astrocytes (ONHAs). Our reconstruction of the molecular interactions affected by glaucoma revealed multi-domain biological networks controlling activation of ONHAs at the level of intercellular stimuli, intracellular signaling and core effectors. The analysis revealed that synergistic action of the transcription factors AP-1, vitamin D receptor and Nuclear Factor-kappaB in cross-activation of multiple pathways, including inflammatory cytokines, complement, clusterin, ephrins, and multiple metabolic pathways. We found that the products of over two thirds of genes linked to glaucoma by
TY - JOUR. T1 - Glutamate transporter function of rat hippocampal astrocytes is impaired following the global ischemia. AU - Yeh, Tu Hsueh. AU - Hwang, Hwa Min. AU - Chen, Jin Jung. AU - Wu, Tony. AU - Li, Allen Hon Lun. AU - Wang, Hung Li. PY - 2005/4. Y1 - 2005/4. N2 - Astroglial glutamate transporters, GLT-1 and GLAST, play an essential role in removing released glutamate from the extracellular space and are essential for maintaining a low concentration of extracellular glutamate in the brain. It was hypothesized that impaired function of glial glutamate transporters induced by transient global ischemia may lead to an elevated level of extracellular glutamate and subsequent excitotoxic neuronal death. To test this hypothesis, in the present study, we performed whole-cell patch-clamp recording of hippocampal CA1 astrocytes in control or postischemic slices, and measured glutamate transporter activity by recording glutamate-evoked transporter currents. Six to 24 h after global ischemia, maximal ...
Objective:To investigate the expression of two-pore domain potassium channel-TREK-1 on primary cultured neurons and astrocytes and the temporal changes of TREK-1 expression in astrocytes under hypoxia insult.Methods: The cortical neurons and astrocytes were cultured.The expression of TREK-1 in cultured neurons and astrocytes were analyzed by double immunofluorescence staining.The temporal changes of TREK-1 expression in astrocytes under hypoxia insults were detected by Real-time PCR.Results: The TREK-1 immuno-reactivity was expressed on both the neurons and astrocytes under normal condition.During hypoxia insult,the TREK-1 expression on astrocyte increases at early phases and decreases gradually at late phase.Conclusion: The TREK-1 immunoreactivity is expressed on both the neurons and astrocytes.In astrocytes under hypoxia,there are temporal changes on TREK-1 expression.
Glial Fibrillary Acid Protein (GFAP) Mouse, Alexa Fluor 488, Clone: GA5, eBioscience™ 25μg; Alexa Fluor 488 Glial Fibrillary Acid Protein (GFAP) Mouse, Alexa...
TY - JOUR. T1 - Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS. AU - Chen, Meifan. AU - Geoffroy, Cédric G.. AU - Meves, Jessica M.. AU - Narang, Aarti. AU - Li, Yunbo. AU - Nguyen, Mallorie T.. AU - Khai, Vung S.. AU - Kong, Xiangmei. AU - Steinke, Christopher L.. AU - Carolino, Krislyn I.. AU - Elzière, Lucie. AU - Goldberg, Mark P.. AU - Jin, Yishi. AU - Zheng, Binhai. PY - 2018/3/27. Y1 - 2018/3/27. N2 - Reactive astrocytes influence post-injury recovery, repair, and pathogenesis of the mammalian CNS. Much of the regulation of astrocyte reactivity, however, remains to be understood. Using genetic loss and gain-of-function analyses in vivo, we show that the conserved MAP3K13 (also known as leucine zipper-bearing kinase [LZK]) promotes astrocyte reactivity and glial scar formation after CNS injury. Inducible LZK gene deletion in astrocytes of adult mice reduced astrogliosis and impaired glial scar formation, resulting in increased ...
Astrocytes play many roles essential for normal brain activity. The ability of these cells to recover after temporary focal cerebral ischemia is likely to be one important determinant of the extent of brain dysfunction and tissue damage. We have assessed astrocytic function based on the incorporation of radiolabel from 1-14C-acetate into glutamine at 1 hour of recirculation after middle cerebral artery occlusion for 2 or 3 hours in rats. There were marked differences in the response between subregions within the tissue subjected to ischemia, but the overall pattern of changes was similar after each ischemic period. The striatum, which forms part of the severely ischemic focal tissue during arterial occlusion, showed a large (44% to 68%) decrease in glutamine labeling compared with equivalent tissue from the contralateral hemisphere. In contrast, 14C-glutamine content was not significantly altered in perifocal tissue in the cerebral cortex, which was subjected to more moderate ischemia. Cortical ...
Purpose To determine whether optic nerve head (ONH) astrocytes, a key cellular component of glaucomatous neuropathy, exhibit differential gene expression in primary cultures of astrocytes from normal African American (AA) donors compared to astrocytes from normal Caucasian American (CA) donors. Methods We used oligonucleotide Affymetrix microarray (HG U133A & HG U133A 2.0 chips) to compare gene expression levels in cultured ONH astrocytes from twelve CA and twelve AA normal age matched donor eyes. Chips were normalized with Robust Microarray Analysis (RMA) in R using Bioconductor. Significant differential gene expression levels were detected using mixed effects modeling and Statistical Analysis of Microarray (SAM). Functional analysis and Gene Ontology were used to classify differentially expressed genes. Differential gene expression was validated by quantitative real time RT-PCR. Protein levels were detected by Western blots and ELISA. Cell adhesion and migration assays tested physiological responses.
Purpose: Retinal neovascularization has been intensively investigated in the mouse model of oxygen-induced retinopathy (OIR). The role of astrocytes for vascular loss and reactive angiogenesis, however, is not fully understood. Due to their stellar morphology, only semi-quantitative analysis has yet been possible. This study presents data on the kinetics of retinal astrocytes in relation to changes in the vascular bed during the OIR model based on a quantitative approach.. Methods: In the OIR model, mice are exposed to 75% oxygen from post-natal day 7 (P7) to P12 (hyperoxic phase). After return to room air, the avascular area of the retina becomes hypoxic and responds with physiologic and pathologic revascularization from P12 to P21. In this study, reporter mice expressing histone-bound GFP under the control of the Pdgfra promoter were used to identify astrocyte nuclei in the murine retina. The astrocytic density across the retina was determined at different times during the OIR model using the ...
Background The efficient derivation of mature (Hb9+) motor neurons from embryonic stem cells is a sought-after goal in the understanding, and potential treatment, of motor neuron diseases. Conditions that promote the robust generation of motor neuron progenitors from embryonic stem cells and that promote the survival of differentiated motor neurons ex vivo are likely, therefore, to be critical in future biological/therapeutic/screening approaches. Previous studies have shown that astrocytes have a protective effect on differentiated motor neurons (in vivo and ex vivo), but it remains unclear whether astrocytes also play a beneficial role in the support of motor neuron progenitors. Here we explore the effect of murine astrocyte-conditioned medium on monolayer cultures of mouse embryonic stem cell-derived motor neuron progenitors. Results Our data show that wild-type astrocyte-conditioned medium significantly increases the number of Olig2+/Hb9- progenitors, which subsequently differentiate into ...
Neurons have intrinsic capability to regenerate after lesion, though not spontaneously. Spinal cord injury (SCI) causes permanent neurological impairments partly due to formation of a glial scar that is composed of astrocytes and microglia. Astrocytes play both beneficial and detrimental roles on axonal re-growth, however, their precise role after SCI is currently under debate. We analyzed molecular changes in astrocytes at multiple stages after two SCI severities using cell-specific transcriptomic analyses. We demonstrate that astrocyte response after injury depends on both time after injury and lesion severity. We then establish that injury induces an autologous astroglial transdifferentiation where over 10 % of astrocytes express classical neuronal progenitor markers including βIII-tubulin and doublecortin with typical immature neuronal morphology. Lineage tracing confirmed that the origin of these astrocytes is resident mature, rather than newly formed astrocytes. Astrocyte-derived neuronal
AbstractBackgroundNeurons have intrinsic capability to regenerate after lesion, though not spontaneously. Spinal cord injury (SCI) causes permanent neurological impairments partly due to formation of a glial scar that is composed of astrocytes and microglia. Astrocytes play both beneficial and detrimental roles on axonal re-growth, however, their precise role after SCI is currently under debate.MethodsWe analyzed molecular changes in astrocytes at multiple stages after two SCI severities using cell-specific transcriptomic analyses.ResultsWe demonstrate that astrocyte response after injury depends on both time after injury and lesion severity. We then establish that injury induces an autologous astroglial transdifferentiation where over 10 % of astrocytes express classical neuronal progenitor markers including βIII-tubulin and doublecortin with typical immature neuronal morphology. Lineage tracing confirmed that the origin of these astrocytes is resident mature, rather than newly formed astrocytes.
TY - JOUR. T1 - Iron uptake in quiescent and inflammation-activated astrocytes. T2 - A potentially neuroprotective control of iron burden. AU - Pelizzoni, Ilaria. AU - Zacchetti, Daniele. AU - Campanella, Alessandro. AU - Grohovaz, Fabio. AU - Codazzi, Franca. PY - 2013/8. Y1 - 2013/8. N2 - Astrocytes play a crucial role in proper iron handling within the central nervous system. This competence can be fundamental, particularly during neuroinflammation, and neurodegenerative processes, where an increase in iron content can favor oxidative stress, thereby worsening disease progression. Under these pathological conditions, astrocytes undergo a process of activation that confers them either a beneficial or a detrimental role on neuronal survival. Our work investigates the mechanisms of iron entry in cultures of quiescent and activated hippocampal astrocytes. Our data confirm that the main source of iron is the non-transferrin-bound iron (NTBI) and show the involvement of two different routes for its ...
Optic nerve regeneration (ONR) following injury is a model for central nervous system regeneration. In zebrafish, ONR is rapid - neurites cross the lesion and enter the optic tectum within 7 days; in mammals regeneration does not take place unless astrocytic reactivity is suppressed. Glial fibrillary acidic protein (GFAP) is used as a marker for retinal and optic nerve astrocytes in both fish and mammals, even though it has long been known that astrocytes of optic nerves in many fish, including zebrafish, express cytokeratins and not GFAP. We used immunofluorescence to localize GFAP and cytokeratin in wild-type zebrafish and transgenic zebrafish expressing green fluorescent protein (GFP) under control of a GFAP promoter to determine the pattern of expression of intermediate filaments in retina and optic nerve. GFAP labeling and GFAP gene expression as indicated by GFP fluorescence was found only in the Müller glial cells of the retina. Within Müller cells, GFP fluorescence filled the entire cell while
BACKGROUND: Reactive astrogliosis is a ubiquitous but poorly understood hallmark of central nervous system pathologies such as trauma and neurodegenerative diseases. In vitro and in vivo studies have identified proinflammatory cytokines and chemokines as mediators of astrogliosis during injury and disease; however, the molecular mechanism remains unclear. In this study, we identify astrocyte elevated gene-1 (AEG-1), a human immunodeficiency virus 1 or tumor necrosis factor alpha-inducible oncogene, as a novel modulator of reactive astrogliosis. AEG-1 has engendered tremendous interest in the field of cancer research as a therapeutic target for aggressive tumors. However, little is known of its role in astrocytes and astrocyte-mediated diseases. Based on its oncogenic role in several cancers, here we investigate the AEG-1-mediated regulation of astrocyte migration and proliferation during reactive astrogliosis. METHODS: An in vivo brain injury mouse model was utilized to show AEG-1 induction ...
Background: Neurons have intrinsic capability to regenerate after lesion, though not spontaneously. Spinal cord injury (SCI) causes permanent neurological impairments partly due to formation of a glial scar that is composed of astrocytes and microglia. Astrocytes play both beneficial and detrimental roles on axonal re-growth, however, their precise role after SCI is currently under debate. Methods: We analyzed molecular changes in astrocytes at multiple stages after two SCI severities using cell-specific transcriptomic analyses. Results: We demonstrate that astrocyte response after injury depends on both time after injury and lesion severity. We then establish that injury induces an autologous astroglial transdifferentiation where over 10 % of astrocytes express classical neuronal progenitor markers including beta III-tubulin and doublecortin with typical immature neuronal morphology. Lineage tracing confirmed that the origin of these astrocytes is resident mature, rather than newly formed ...
Background: HIV-1 infected individuals are under chronic exposure to reactive oxygen species (ROS) considered to be instrumental in the progression of AIDS and the development of HIV-1 associated dementia (HAD). Astrocytes support neuronal function and protect them against cytotoxic substances including ROS. The protein HIV-1 Nef, a progression factor in AIDS pathology is abundantly expressed in astrocytes in patients with HAD, and thus may influence its functions. Results: Endogenous expressed HIV-1 Nef leads to increased sensitivity of human astrocytes towards exogenous hydrogen peroxide but not towards TNF-alpha. Cell death of nef-expressing astrocytes exposed to 10 mu M hydrogen peroxide for 30 min occurred within 4 h. Conclusion: HIV-1 Nef may contribute to neuronal dysfunction and the development of HAD by causing death of astrocytes through decreasing their tolerance for hydrogen peroxide. ...
Abstract: A glutamate hypothesis of schizophrenia emerged based on pharmacological evidence that N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine (PCP), can induce symptoms similar to those seen in schizophrenia. Subsequently, abnormal expression of various neuronal molecules associated with the glutamate synapse has been reported in schizophrenia. Astrocytes, a prominent glial cell in the brain, play a significant role in maintaining the structure and integrity of neural tissue and in facilitating excitatory neurotransmission, therefore, any breakdown in the structure or function of astrocytes could disrupt neuronal signaling and disturb brain function. I studied structural and functional molecules in astrocytes to determine 1) whether astrocytes are themselves globally compromised in schizophrenia, and 2) whether abnormal expression of glutamatergic molecules in astrocytes could be a contributing factor to brain dysfunction in this illness. I examined the expression of ...
TY - JOUR. T1 - D-serine, an endogenous synaptic modulator. T2 - Localization to astrocytes and glutamate-stimulated release. AU - Schell, Michael J.. AU - Molliver, Mark E.. AU - Snyder, Solomon H.. PY - 1995/4/25. Y1 - 1995/4/25. N2 - Using an antibody highly specific for D-serine conjugated to glutaraldehyde, we have localized endogenous D-serine in rat brain. Highest levels of D-serine immunoreactivity occur in the gray matter of the cerebral cortex, hippocampus, anterior olfactory nucleus, olfactory tubercle, and amygdala. Localizations of D-serine immunoreactivity correlate closely with those of D-serine binding to the glycine modulatory site of the N-methyl-D- aspartate (NMDA) receptor as visualized by autoradiography and are inversely correlated to the presence of D-amino acid oxidase. D-Serine is enriched in process-bearing glial cells in neuropil with the morphology of protoplasmic astrocytes. In glial cultures of rat cerebral cortex, D-serine is enriched in type 2 astrocytes. The ...
Clone REA335 recognizes the human, mouse, and rat glial fibrillary acidic protein (GFAP), the main intermediate filament protein in mature astrocytes and an important component of the cytoskeleton in astrocytes during development. GFAP is expressed exclusively in astrocytes in the central nervous system. It has been shown to be involved in astrocyte functions, which are important during regeneration, synaptic plasticity, and reactive gliosis. Moreover, different subpopulations of astrocytes have been identified, which are likely to have distinctive tasks in brain physiology and pathology, and which are not only classified by their spatial and temporal appearance, but also by their specific expression of intermediate filaments, including distinct GFAP isoforms. Additional information: Clone REA335 displays negligible binding to Fc receptors. - Österreich
The central nervous system (CNS) is arguably the most important part of the human body. It includes the brain and the spinal cord. The brain is widely believed to be where all our thought originate. It compares and contrasts. It strings together words and paragraphs. It helps us to understand and communicate with the world around us. Given the complexity of this remarkable organ, it is hardly surprising that we are still uncovering its secrets. One such secret is the important role of astrocytes.. The brain isnt only occupied by neurons. Glial cells are also a local inhabitant. Though long thought to be little more than the neurons sidekicks, we now know that glial cells are a crucial component of CNS operations. Astrocytes are one of four identified glial cells in the CNS. Two additional varieties hang out in the periphery nervous system.. Astrocytes are essential for maintaining homeostasis in the CNS. They also play a role In brain defense and rejuvenation. Their malfunction or retardation ...
Cell culture: monocultures. Primary human fetal astrocyte cultures were established from 3 different brains as previously described (67). We confirmed an identical in vitro phenotype of commercially available cells (Lonza) and cross-referenced these to previous phenotypes. To establish human CD3+ T lymphocyte cultures from human blood of healthy donors, density centrifugation using Ficoll-Paque PLUS (GE Healthcare) was initially performed to isolate peripheral blood mononuclear cells (PBMCs) from whole blood. Six milliliters of whole blood containing acid citrate dextrose anticoagulant (Biological Specialty Corp.) was diluted with an equal volume of HBSS (Mediatech Inc.) and carefully layered in 15-ml tubes prefilled with 4 ml of density gradient medium. Tubes were centrifuged 40 minutes at 900 relative centrifugal force (RCF). PBMCs were collected by transfer pipette and afterward washed 2-3 times in HBSS (Mediatech Inc.) and centrifuged 15 minutes at 250 RCF. Human CD3+ T lymphocytes were then ...
Cell culture: monocultures. Primary human fetal astrocyte cultures were established from 3 different brains as previously described (67). We confirmed an identical in vitro phenotype of commercially available cells (Lonza) and cross-referenced these to previous phenotypes. To establish human CD3+ T lymphocyte cultures from human blood of healthy donors, density centrifugation using Ficoll-Paque PLUS (GE Healthcare) was initially performed to isolate peripheral blood mononuclear cells (PBMCs) from whole blood. Six milliliters of whole blood containing acid citrate dextrose anticoagulant (Biological Specialty Corp.) was diluted with an equal volume of HBSS (Mediatech Inc.) and carefully layered in 15-ml tubes prefilled with 4 ml of density gradient medium. Tubes were centrifuged 40 minutes at 900 relative centrifugal force (RCF). PBMCs were collected by transfer pipette and afterward washed 2-3 times in HBSS (Mediatech Inc.) and centrifuged 15 minutes at 250 RCF. Human CD3+ T lymphocytes were then ...
Cambridge, MA, December 11, 2018 - Astrocyte Pharmaceuticals Inc., a privately held pharmaceutical company, today announced that Jeffrey L. Saver, M.D., has joined the companys Scientific Advisory Board and will chair the companys Clinical Advisory Board. Astrocyte Pharmaceuticals is developing small molecule therapeutics for the treatment of brain injuries, including patients who have suffered a stroke, traumatic brain injury (TBI) or concussion.. Dr. Saver is a recognized international thought leader on cerebrovascular research and treatments, with impressive experience in designing and leading multiple, successful, innovative clinical studies in stroke, said William Korinek, CEO at Astrocyte Pharmaceuticals. We are excited to have Dr. Saver chair our Clinical Advisory Board that will design the optimal clinical studies to assess AST-004s efficacy in human patients.. Dr. Jeffrey Saver is Vice-Chair and Professor of Neurology at the David Geffen School of Medicine at UCLA and has been ...
The study in mice, by neuroscientists at Tufts University School of Medicine, determined that astrocytes play a critical role in the spread of damage following stroke.. The National Heart Foundation reports that ischemic strokes account for 87% of strokes in the United States. Ischemic strokes are caused by a blood clot that forms and travels to the brain, preventing the flow of blood and oxygen.. Even when blood and oxygen flow is restored, however, neurotransmitter processes in the brain continue to overcompensate for the lack of oxygen, causing brain cells to be damaged. The damage to brain cells often leads to health complications including visual impairment, memory loss, clumsiness, moodiness, and partial or total paralysis.. Research and drug trials have focused primarily on therapies affecting neurons to limit brain cell damage. Phil Haydons group at Tufts University School of Medicine have focused on astrocytes, a lesser known type of brain cell, as an alternative path to understanding ...
According to previous studies, miRNAs affect astrogliosis and astrocyte proliferation through targetting diverse downstream genes [22,26]. To investigate the mechanism by which BDNF affects NHA proliferation, we used online tools including Tarbase and miRWalk to search for the candidate miRNAs which might regulate BDNF expression. After cross-contrast with the results of two software predictions, 14 candidate miRNAs were chosen for further verification (miR-15b, miR-497, miR-211, miR-206, miR-195, miR-204, miR-1s, miR-382, miR-613, miR-15a, miR-16, miR-103a, miR-182, and miR-107, Figure 3A). Upon LPS stimulation, the expression of the indicated candidate miRNAs was monitored; amongst all the candidate miRNAs, miR-211 expression was inhibited by LPS stimulation in a dose-dependent manner (Figure 3B). Next, we verified miR-211 regulation of BDNF using qRT-PCR and Western blot assays. In miR-211 mimics transfected NHAs, BDNF mRNA and protein levels were significantly reduced, whereas miR-211 ...
Lesions and neurologic disability in inflammatory CNS diseases such as multiple sclerosis (MS) result from the translocation of leukocytes and humoral factors from the vasculature, first across the endothelial blood-brain barrier (BBB) and then across the astrocytic glia limitans (GL). Factors secreted by reactive astrocytes open the BBB by disrupting endothelial tight junctions (TJs), but the mechanisms that control access across the GL are unknown. Here, we report that in inflammatory lesions, a second barrier composed of reactive astrocyte TJs of claudin 1 (CLDN1), CLDN4, and junctional adhesion molecule A (JAM-A) subunits is induced at the GL. In a human coculture model, CLDN4-deficient astrocytes were unable to control lymphocyte segregation. In models of CNS inflammation and MS, mice with astrocyte-specific Cldn4 deletion displayed exacerbated leukocyte and humoral infiltration, neuropathology, motor disability, and mortality. These findings identify a second inducible barrier to CNS entry ...
0066]Astroglia cells, i.e. non neoplastic embryonal astrocyte cell line of the rat [Chamaon, K., Kirches, E., Kanakis, D., Braeuninger, S., Dietzmann, K., and Mawrin, C. (2005). Regulation of the pituitary tumor transforming gene by insulin-like-growth factor-I and insulin differs between malignant and non-neoplastic astrocytes. Biochem Biophys Res Commun 331, 86-92] were cultivated on glass cover slips coated with poly-D-lysin at the bottom of culture dishes at 37° C. during 18 hours (5% CO2). 2 ml DMEM (PAA Laboratories GmbH Pasching, Austria) were used as the culture medium in each reaction and the sowing density was 0.3×106 cells/2 ml. First, the cell cultures were pre-incubated in different concentrations (1.0; 5.0 or 25.0 μM) of minocycline hydrochloride or pentaacetyl cyclin (Formula II) during 30 minutes. The sole addition of the solvent DMSO (2 μl/culture dish) under identical incubation conditions was used as the untreated control. Then, 1.0 or 3.0 mM H2O2 (final concentration) was ...
The type beta transforming growth factors (TGF) are potent regulators of the growth and functions of lymphocytes and macrophages. Recently the human glioblastoma cell line 308 was shown to produce TGF-beta 2. The relevance of this finding was evaluated further by comparing human glioblastoma cells with their nontransformed animal counterpart, astrocytes, with regard to the production of the three TGF-beta isoforms observed so far in mammals. In this report astrocytes are demonstrated to secrete also TGF-beta 2 and to express TGF-beta 1, -beta 2, and -beta 3 mRNA in vitro. In contrast, cultured murine brain macrophages release TGF-beta 1 and are positive for TGF-beta 1 mRNA only. Glia cell-derived TGF-beta 1 and -beta 2 are detected in latent form whereas both latent and active TGF-beta are identified in the supernatant of three human glioblastoma cell lines tested. These cell lines, however, show heterogeneity in regard to the isoform of TGF-beta expressed but share with astrocytes the inability ...
Interneurons are critical for proper neural network function and can activate Ca2+ signaling in astrocytes. However, the impact of the interneuron-astrocyte signaling into neuronal network operation remains unknown. Using the simplest hippocampal Astrocyte-Neuron network, i.e., GABAergic interneuron, pyramidal neuron, single CA3-CA1 glutamatergic synapse, and astrocytes, we found that interneuron-astrocyte signaling dynamically affected excitatory neurotransmission in an activity- and time-dependent manner, and determined the sign (inhibition vs potentiation) of the GABA-mediated effects. While synaptic inhibition was mediated by GABAA receptors, potentiation involved astrocyte GABAB receptors, astrocytic glutamate release, and presynaptic metabotropic glutamate receptors. Using conditional astrocyte-specific GABAB receptor (Gabbr1) knockout mice, we confirmed the glial source of the interneuron-induced potentiation, and demonstrated the involvement of astrocytes in hippocampal theta and gamma ...
Neuroinflammation is an essential defense response to pathogens or injury in the central nervous system, but might also contribute to the pathogenesis of neurological disorders. Astrocytes are glial cells that are implicated in neuroinflammation, but also in brain development and homeostasis. The NF-kappa B transcription factors are key regulators of inflammation that also regulate in cell proliferation, differentiation and survival. Previous studies suggested that NF-kappa B activation in astrocytes might indeed be critical for neuroinflammatory responses and its pathological consequences. In the present study a novel mouse model was characterized to further elucidate the role of astroglial NF-Kappa B signaling in neuroinflammation. This model conditionally expresses a constitutively active mutant of the NF-kappa B activating kinase IKK2 in astrocytes. This results in astroglial NF-kappa B activation, which is sufficient to induce a prominent neuroinflammatory response and impairs brain ...
Neuroinflammation is an essential defense response to pathogens or injury in the central nervous system, but might also contribute to the pathogenesis of neurological disorders. Astrocytes are glial cells that are implicated in neuroinflammation, but also in brain development and homeostasis. The NF-kappa B transcription factors are key regulators of inflammation that also regulate in cell proliferation, differentiation and survival. Previous studies suggested that NF-kappa B activation in astrocytes might indeed be critical for neuroinflammatory responses and its pathological consequences. In the present study a novel mouse model was characterized to further elucidate the role of astroglial NF-Kappa B signaling in neuroinflammation. This model conditionally expresses a constitutively active mutant of the NF-kappa B activating kinase IKK2 in astrocytes. This results in astroglial NF-kappa B activation, which is sufficient to induce a prominent neuroinflammatory response and impairs brain ...
Supplementary MaterialsSupplementary Information 41467_2020_14466_MOESM1_ESM. following faraway cortical brain injury in mice. Fibrinogen inhibited neuronal differentiation in SVZ and hippocampal NSPCs while promoting astrogenesis via activation of the BMP receptor signaling pathway. Pharmacologic and Genetic depletion of fibrinogen reduced astrocyte formation within the SVZ after cortical injury, reducing the contribution of NVP-2 SVZ-derived reactive astrocytes to lesion scar tissue formation. We suggest that fibrinogen can be a regulator of NVP-2 NSPC-derived astrogenesis through the SVZ market via BMP receptor signaling pathway pursuing damage. transgenic reporter mice in conjunction with pharmacologic fibrinogen depletion exposed decreased contribution NVP-2 of SVZ-derived Thbs4?+?reactive astrocytes to lesion scar formation. Appropriately, fibrinogen inhibited neuronal differentiation of NVP-2 major NSPCs through the SVZ or hippocampus and advertised their differentiation into astrocytes ...
Aspirin has been used as anti-inflammatory and anti-aggregate for decades but the precise mechanism(s) of action after the presence of the toxic peptide Aβ1-42 in cultured astrocytes remains poorly resolved. Here we use low-doses of aspirin (10-7 M) in astrocytes in primary culture in presence or absence of Aβ1-42 toxic peptide. We noted an increase of cell viability and proliferation with or without Aβ1-42 peptide presence in aspirin treated cells. In addition, a decrease in apoptosis, determined by Caspase 3 activity and the expression of Cyt c and Smac/Diablo, were detected. Also, aspirin diminished necrosis process (LDH levels), pro-inflammatory mediators (IL-β and TNF-α) and NF-ᴋB protein expression, increasing anti-inflammatory PPAR-γ protein expression, preventing Aβ1-42 toxic effects. Aspirin inhibited COX-2 and iNOS without changes in COX-1 expression, increasing anti-oxidant protein (Cu/Zn-SOD and Mn-SOD) expression in presence or absence of Aβ1-42. Taken together, our ...
The energy requirements of the brain are very high, and tight regulatory mechanisms operate to ensure adequate spatial and temporal delivery of energy substrates in register with neuronal activity. Astrocytes a type of glial cell have emerged as active players in brain energy delivery, production, utilization, and storage. Our understanding of neuroenergetics is rapidly evolving from a neurocentric view to a more integrated picture involving an intense cooperativity between astrocytes and neurons. This review focuses on the cellular aspects of brain energy metabolism, with a particular emphasis on the metabolic interactions between neurons and astrocytes.. Keywords: Nuclear-Magnetic-Resonance ; Cerebral-Blood-Flow ; Vasoactive Intestinal Polypeptide ; Lactate-Shuttle Hypothesis ; Human Visual-Cortex ; Rat-Brain ; Glucose-Utilization ; Nitric-Oxide ; In-Vivo ; Oxidative-Metabolism. ...
The release of transmitters from glia influences synaptic functions. The modalities and physiological functions of glial release are poorly understood. Here we show that glutamate exocytosis from astrocytes of the rat hippocampal dentate molecular layer enhances synaptic strength at excitatory synap …
Figure 1. Live imaging of neuronal differentiation. Ravin, et al, used SBIs Human Nestin pGreenFire Differentiation Reporter (Cat.# SR10016VA-1), which drives GFP expression from the glial fibrillary acidic protein promoter, to watch human neural stem cells differentiate into a network of mature neurons, oligodendrocytes, and astrocytes over the course of seven days. The periodic flashes seen in this video correspond to fluorescent photos taken of the growing cells to identify the GFP signals. The final photo taken after the network formation is shown below the video (color added). Among the network of neurons, only the astrocytes are bright green, demonstrating the specificity of SBIs human Nestin pGreenFire Differentiation Reporter.. ...
Support Cells. Neurons in the CNS are outnumbered by support cells, including macroglia, microglia, vascular elements, the cerebrospinal fluid (CSF)-forming cells of the choroid plexus found within the intracerebral ventricular system, and the meninges, which cover the surface of the brain and comprise the CSF-containing envelope. Macroglia are the most abundant support cells; some are categorized as astrocytes (cells interposed between the vasculature and the neurons, often surrounding individual compartments of synaptic complexes). Astrocytes play a variety of metabolic support roles including furnishing energy intermediates and supplementary removal of neurotransmitters following release. The oligodendroglia, a second prominent category of macroglia, are myelin-producing cells. Myelin, made up of multiple layers of compacted membranes, insulate segments of axons bioelectrically and permit nondecremental propagation of action potentials. Microglia are derived from mesoderm and are related to ...
Astrocyte Research launches Portformer™ Competitor Intelligence tool in private beta for ETF and mutual fund issuers.. BOSTON, MA, July 31, 2019 - Astrocyte Research launches Portformer™ Competitor Intelligence. This browser-based application maps the investment landscape through dynamic, intuitive visualizations powered by machine learning. Clients can explore fund-to-fund comparisons or view high-level fund lineup relationships.. Competitor Intelligence allows sales teams to demonstrate the value of their products to potential clients, while executives discover opportunities to win assets and protect against outflows to competing funds. Portformer™ Competitor Intelligence helps medium to small fund issuers differentiate their innovative and efficient products.. Investors want diversified and efficient investments, says Astrocyte Research CEO Sean Kruzel, but decision-making has mostly centered on branding and price. By uncovering which funds are really earning their fees, we can get ...
Mulvihill, J.J.E. and Raykin, J. and Snider, E.J. and Schildmeyer, L.A. and Zaman, I. and Platt, M.O. and Kelly, D.J. and Ethier, C.R., Development of a Platform for Studying 3D Astrocyte Mechanobiology: Compression of Astrocytes in Collagen Gels, Annals of Biomedical Engineering, 46, 2, 2018, 365?374 ...
In this Application, we describe a protocol to generate highly purified and viable astrocytes from neonatal mouse brain tissue. - France
This chapter focuses on the role of neurogenic astroglial cells in the development of the central nervous system (CNS). Recent findings have elucidated a more complex role for astroglial cells in the development of CNS structures across many species. Mitotically active radial glial cells line the ventricular system throughout the developing CNS and have been shown to generate neocortical neurons in rodents. Precursor cells in the ventricular zone (VZ) can divide symmetrically or asymmetrically, and evidence indicates that both types of divisions coexist throughout the entire period of cortical neurogenesis. ...
Rouach, N.; Glowinski, J.; Giaume, C. (2000). "Astrocytes". The Journal of Cell Biology. 149 (7): 1513-1526. doi:10.1083/jcb. ... properties of astrocytes and astrocyto-neuronal relationships, Parkinson's disease, schizophrenia, drug addiction, ...
... s differentiate into astrocytes and oligodendrocytes. Its tumor is called a glioblastoma multiforme, and is the most ...
It appears that astrocytes are coupled by gap junctions, both to other astrocytes and to oligodendrocytes. Moreover, mutations ... Orthmann-Murphy, Jennifer L.; Abrams, Charles K.; Scherer, Steven S. (May 2008). "Gap Junctions Couple Astrocytes and ... with antibodies against external loop domains in astrocytes". Glia. 24 (1): 141-54. doi:10.1002/(SICI)1098-1136(199809)24:1. ...
"Aged Astrocytes Prime Brain for Neuroinflammation , ALZFORUM". www.alzforum.org. Retrieved 2020-03-07. "Astrocytes Are Trusty ... In 2012 while she was a postdoc in the lab of Ben Barres, she showed that astrocytes secrete glypican 4 and 6, which is needed ... "Brain cells called astrocytes have unexpected role in brain "plasticity"". Salk Institute for Biological Studies. Retrieved ... Allen also showed that astrocytes excrete a protein called Chrdl1, which helps the maturation of the brain. It also increased ...
Wang, Doris D.; Bordey, Angélique (11 December 2008). "The astrocyte odyssey". Progress in Neurobiology. 86 (4): 342-367. doi: ... which also contain other cell types including astrocytes and microglia in the CNS and macrophages in the PNS. In terms of total ... by the processes of another type of glial cell called the astrocyte.[citation needed] CNS myelin differs slightly in ...
Astrocytes help to maintain ionic balance in the extracellular space in the brain. Knock-out of PMCA2 causes inner ear problems ... PMCA types 1, 2, and 4 have been found in glial cells called astrocytes in mammals, though it was previously thought that only ... "Plasma membrane calcium ATPase isoforms in astrocytes". Glia (published 1999-10-22). 28 (2): 150-155. doi:10.1002/(SICI)1098- ...
... these astrocytes are found in close proximity to the 'end feet' of blood vessels. These astrocytes aid in the tightening and ... The crucial role that astrocytes play in the formation of muscle memory may also shed light on the beneficial impact of ... Lundgaard, I.; Osório, M.J.; Kress, B.T.; Sanggaard, S.; Nedergaard, M. (2014). "White matter astrocytes in health and disease ... Gold, Paul E. (2014). "Regulation of memory - from the adrenal medulla to liver to astrocytes to neurons". Brain Research ...
Around the edge of necrosis, astrocytes proliferate. These cells extend processes, and form a delicate rim of gliosis around ...
Colin, A (2009). "Engineered lentiviral vector targeting astrocytes in vivo". Glia. 57 (6): 667-679. doi:10.1002/glia.20795. ...
Astrocytes then cause the toxic effects on the motor neurons. The specific mechanism of toxicity still needs to be investigated ... Nagai M, Re DB, Nagata T, Chalazonitis A, Jessell TM, Wichterle H, Przedborski S (May 2007). "Astrocytes expressing ALS-linked ... Julien JP (May 2007). "ALS: astrocytes move in as deadly neighbors". Nature Neuroscience. 10 (5): 535-7. doi:10.1038/nn0507-535 ... research provided in vitro evidence that the primary cellular sites where SOD1 mutations act are located on astrocytes. ...
Fañanas cells are sometimes defined as "specialised astrocytes". The feathered cells are named after Jorge Ramón y Cajal ... of the study did not point at significant mutations in Fañanas cells but rather described the possible importance of astrocytes ...
Such astrocytes are also known as gemistocytic astrocytes. Gemistocytes are also found in some chronic diseases and within ... Astrocytes participating in gliosis are referred to as reactive astrocytes. They have a large cytoplasmic mass, long, branching ... A gemistocyte (/dʒɛˈmɪstəsaɪt/ jem-ISS-tə-syte; from Greek γέμιζω (gemizo) 'to fill up') is a swollen, reactive astrocyte. ...
Björklund O, Shang M, Tonazzini I, Daré E, Fredholm BB (2008). "Adenosine A1 and A3 receptors protect astrocytes from hypoxic ... Chronic use of PPIs may cause down regulation of alpha3 subunit increasing damage to astrocytes. Osteopetrosis via TCIRG1 gene ... Memory has been associated with astrocytes and the alpha3 subunit of adenosine receptor found in hydrogen/Sodium-potassium ... Ben Haim L, Carrillo-de Sauvage MA, Ceyzériat K, Escartin C (2015). "Elusive roles for reactive astrocytes in neurodegenerative ...
PEA in this model also reduced the activation of microglia and astrocytes. Its activity as an inhibitor of inflammation ... Nakagawa T, Kaneko S (2010). "Spinal astrocytes as therapeutic targets for pathological pain". Journal of Pharmacological ... July 2011). "Palmitoylethanolamide stimulation induces allopregnanolone synthesis in C6 Cells and primary astrocytes: ...
... remove ERα from astrocytes. It was found that the mice with ERα knocked out in astrocytes experienced an increase in clinical ... In a 2011 research article, Voskuhl published data revealing that the estrogen receptor α (ERα) on astrocytes, not neurons, was ... "Neuroprotection mediated through estrogen receptor-α in astrocytes". Proceedings of the National Academy of Sciences of the ...
He also found that large populations of astrocytes negative to classical marker GFAP but positive to glutamine synthetase or ... Subsequently, he identified a unique expression of highly ATP-sensitive P2X1/5 receptors in cortical astrocytes and ... First, in collaboration with Rodriguez, he discovered prominent inhibition of neurogenesis (linked to the radial astrocytes- ... After moving to Manchester, Verkhratsky focused on astroglia and characterised various aspects of astrocyte membrane physiology ...
Astrocytes also exchange information with the synaptic neurons, responding to synaptic activity and, in turn, regulating ... Perea, G.; Navarrete, M.; Araque, A. (August 2009). "Tripartite synapses: astrocytes process and control synaptic information ...
The ependymal cells and astrocytes form glial tubes used by migrating neuroblasts. The astrocytes in the tubes provide support ... The astrocytes are the primary precursors for rapid cell amplification. The neuroblasts form tight chains and migrate towards ... Reynolds, B.; Weiss, S (1992). "Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous ... NSCs have an important role during development producing the enormous diversity of neurons, astrocytes and oligodendrocytes in ...
Rycerz K, Jaworska-Adamu JE (2013). "Effects of aspartame metabolites on astrocytes and neurons". Folia Neuropathologica. 51 (1 ...
Reactive astrocytes are related to the normal function of astrocytes. Astrocytes are involved in the complex regulation of CNS ... Astrocytes interact extensively with microglia and play a key role in CNS inflammation. Reactive astrocytes can then lead to ... Loss or disturbance of functions normally performed by astrocytes or reactive astrocytes during the process of reactive ... Mature astrocytes can re-enter the cell cycle and proliferate during scar formation. Some proliferating reactive astrocytes can ...
Teismann, P; Schulz, JB (Oct 2004). "Cellular pathology of Parkinson's disease: astrocytes, microglia and inflammation". Cell ...
"Transfer of mitochondria from astrocytes to neurons after stroke". Nature. 535 (7613): 551-555. Bibcode:2016Natur.535..551H. ...
They are also present on both astrocytes and oligodendrocytes. Ionotropic and metabotropic glutamate receptors, with the ... Furthermore, brain slices show glutamate receptors are ubiquitously expressed in both developing and mature astrocytes and ... in affected neurons and astrocytes, and depolarization increases downstream synaptic release of glutamate. In addition, cell ...
In the neocortex exists a wide neuronal network, supported by astrocytes and oligodendrocytes (glial cells) with different ... Glial progenitor cells could differentiate into oligodendrocytes or astrocytes. However, lineage commitment of neural ... an astrocyte or an oligodendrocyte. High levels of Ngn1 and Ngn2 are required to specify neuronal identity of cortical ...
2001). "Expression of beta-synuclein in normal human astrocytes". NeuroReport. 12 (13): 2845-8. doi:10.1097/00001756-200109170- ...
Astrocytes have also been implicated in multiple sclerosis (MS). Astrocytes are responsible for demyelination and the ... from activated astrocyte cells onto neighboring neurons. Astrocytes that remain in an activated state form glial scars that ... Astrocytes are another type of glial cell that among other functions, modulate the entry of immune cells into the CNS via the ... Astrocytes have many functions in the central nervous system (CNS). ... they are responsible for formation of the blood-brain ...
Bazargani, N; Attwell, D (February 2016). "Astrocyte calcium signaling: the third wave". Nature Neuroscience. 19 (2): 182-9. ... including astrocytes, oligodendrocytes, and microglia. There are many different specialized types of neurons, and their sizes ...
Two main types of astrocytes are found in the SGZ: radial astrocytes and horizontal astrocytes. Radial astrocytes are ... It is not clear whether individual radial astrocytes can play both roles or only certain radial astrocytes can give rise to ... Because astrocytes are in close contact with many of the other cells in the SGZ, they are well-suited to serve as sensory and ... However, unlike most astrocytes, they also act as neurogenic progenitors; in fact, they are widely considered to be the neural ...
Like astrocytes, their cytoplasm presents specific intermediate filaments made up of glial fibrillary acidic protein (GFAP). ... Pituicytes have an irregular and branched shape which resembles that of another type of glial cell: the astrocyte. ... Pituicytes are similar to astrocytes, another type of glial cell. Their main role is to assist in the storage and release of ...
Astrocytes seem to utilize reuptake mechanisms for a neuroprotective role. Astrocytes use excitatory amino acid transporter 2 ( ...
Identification of Astrocyte Markers. To test our assumption that all astrocytes share a common transcriptional profile, we ... All of the astrocyte samples are together. The short vertical distance between the astrocyte samples in the dendrogram ... Of significance, these astrocyte markers revealed surprising molecular heterogeneity among astrocytes in the normal adult brain ... Although expressed in both neurons and astrocytes in culture, it is up-regulated only in astrocytes after cytotoxic stress (26 ...
Astrocyte circadian rhythms depend on clock genes. To assess the molecular basis of circadian timing in astrocytes, we tested ... Astrocytes were derived from mice of different genotypes to assess whether the molecular basis of daily timing in astrocytes is ... 1A,B). Thus, ATP release from murine cortical astrocytes is circadian, consistent with findings in rat astrocytes, immortalized ... For comparison with dnSNARE and VIPP astrocytes, we used astrocytes from wild-type mice or littermates expressing only the ...
In the brain, astrocytes are the most abundant glial cells and play various roles including maintenance of tripartite synapses ... Cette fonctionnalité a été mise à profit pour évaluer la production de NO exclusivement dans les astrocytes en utilisant la ... En conclusion, nos résultats démontrent que : i) les astrocytes corticaux expriment à la fois eNOS et nNOS; ii) la nNOS ... Dans le cerveau, les astrocytes sont les cellules gliales les plus abondantes et elles jouent divers rôles, y compris le ...
We are launching this Research Topic to explore recent advances in understanding how astrocytes listen and speak to neurons to ... With emerging technologies, we have entered a new era of understanding how astrocytes participate in and modulate neuronal ... We are keen to receive submissions on astrocyte functions pertaining to circuits in specific physiological systems towards the ... In particular, we have yet to fully understand: 1) how physiologically and molecularly heterogeneous are astrocytes, 2) how ...
Astrocyte Marker (ab41548) has been cited in 16 publications. References for Mouse, Rat, Pig in Dot, IF, IHC - Wmt, WB ... Bedner P et al. Astrocyte uncoupling as a cause of human temporal lobe epilepsy. Brain 138:1208-22 (2015). PubMed: 25765328 ... Daniels BP et al. Regional astrocyte IFN signaling restricts pathogenesis during neurotropic viral infection. J Clin Invest 127 ...
Because many features of astrocyte development are recapitulated in reactive astrocytes, we investigated the role of nuclear ... Schematic overview of in vitro endothelial/astrocyte barrier assay. (. H. ) NFIA-deficient astrocytes exhibited decreased TEER ... a key transcriptional regulator of astrocyte development whose contributions to reactive astrocytes remain undefined. Here, we ... and a decrease in the expression of the astrocyte endfeet protein Aqp4 (. B. versus D. .) Graphs in E. and F. are derived from ...
... sheds new light on the disruption of astrocytes in depression. Astrocytes, a class of non-neuronal cells, have previously been ... sheds new light on the disruption of astrocytes in depression. Astrocytes, a class of non-neuronal cells, have previously been ... In addition, in describing the existence of new subtypes of astrocyte, this study reveals features specific to the human brain. ... This research provides evidence that networks of astrocytes are altered specifically in areas of the brain associated with mood ...
Treatment of astrocytes with ACT, IL-1beta, or S100beta resulted in glial activation, as assessed by reactive morphology, ... In contrast, BChE alone did not activate astrocytes and had no effect on Abeta-induced activation. These results suggest that ... The ability of Abeta to induce astrocyte activation was also enhanced in the presence of each of these three proteins. ... Glial-derived proteins activate cultured astrocytes and enhance beta amyloid-induced glial activation.. * ...
How might brain "astrocytes" alter nerve cell connections and contribute to Autism Spectrum Disorder? Investigating astrocyte- ... Key functions of astrocytes are altered in some cases of ASD, including Fragile X syndrome where astrocyte transporter function ... Research suggests that astrocytes can produce both advantageous and deleterious effects. In the developing brain, astrocytes ... Astrocytes surround neurons, and their star-shaped "processes" closely associate with synapses enabling astrocytes to ...
The astrocytes next to neurons in the frontal cortex and hippocampus store and release glucose. Thus, astrocytes can fuel ... After astrocyte specification has occurred in the developing CNS, it is believed that astrocyte precursors migrate to their ... When in proximity to the pia mater, all three forms of astrocytes send out processes to form the pia-glial membrane. Astrocytes ... Another study reports that astrocytes are the most numerous cell type in the brain. Astrocytes in humans are more than twenty ...
The astrocytes next to neurons in the frontal cortex and hippocampus store and release glucose. Thus, astrocytes can fuel ... Astrocytes are depicted in red. Cell nuclei are depicted in blue. Astrocytes were obtained from brains of newborn mice ... Astrocytes are macroglial cells in the central nervous system. Astrocytes are derived from heterogeneous populations of ... Gömöri-positive astrocytes. These are a subset of protoplasmic astrocytes that contain numerous cytoplasmic inclusions, or ...
Direct Reprogramming of RESTing Astrocytes.. Wang C1, Fong H1, Huang Y2. ... Transcriptional Mechanisms of Proneural Factors and REST in Regulating Neuronal Reprogramming of Astrocytes. [Cell Stem Cell. ... 2015) use neuronal conversion of astrocytes to dissect transcriptional mechanisms of fate determination and identify circuits ...
Hertz, L. and Schousboe, A., Role of astrocytes in compartmentation of amino acid and energy metabolism. In:Astrocytes, ... Walz, W. and Hinks, E., A transmembrane sodium cycle in astrocytes, Brain Res. 368: 226-232 (1986).PubMedCrossRefGoogle Scholar ... Code, W.E., White, H.S. and Hertz, L., The effect of midazolam on calcium signaling in astrocytes, Ann. N.Y. Acad. Sci. 625: ... Yu, A.C.H., Gregory, G.A. and Chan, P.H., Hypoxia-induced dysfunction and injury of astrocytes in primary cell cultures, J. ...
As evidence of this, astrocytes express protein components of the vesicular secretory a … ... Astrocytes can release a variety of transmitters, including glutamate and ATP, in response to stimuli that induce increases in ... Astrocytes can release a variety of transmitters, including glutamate and ATP, in response to stimuli that induce increases in ... Vesicular transmitter release from astrocytes Glia. 2006 Nov 15;54(7):700-15. doi: 10.1002/glia.20367. ...
Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7-35PubMedCentralPubMedCrossRefGoogle ... Seifert G, Steinhauser C (2013) Neuron-astrocyte signaling and epilepsy. Exp Neurol 244:4-10PubMedCrossRefGoogle Scholar ... Pekny M, Nilsson M (2005) Astrocyte activation and reactive gliosis. Glia 50:427-434PubMedCrossRefGoogle Scholar ... Jo S, Yarishkin O, Hwang YJ, Chun YE, Park M, Woo DH, Bae JY, Kim T, Lee J, Chun H et al (2014) GABA from reactive astrocytes ...
A, two-photon fluorescence image of astrocytes (green) and blood vessels (red) in rat neocortex, stained using the astrocyte- ... Astrocytes going live: advances and challenges.. Nimmerjahn A1.. Author information. 1. Department of Biology, James H. Clark ... C and D, spontaneous calcium transients in two astrocytes (C) and one neuron (D) from a single recording measured as relative ... Astrocytes are one of the most numerous cell types in the CNS. They have emerged as sophisticated cells participating in a ...
MAPK in astrocytes. We also demonstrated that extracellular ATP induces phosphorylation of SAPK/JNK in astrocytes. Experiments ... Vehicle-treated astrocytes show very weak TSP-1 immunoreactivity (Fig. 1 C b and e). Addition of extracellular ATP for 6 h led ... Immunocytochemistry of cultured rat astrocytes after apyrase and ATP treatment. Astrocytes were treated with apyrase (90 units ... B) Astrocytes were treated with 100 μM ATP, 100 μM UTP, 10 μM 2MeSADP, or 100 μM adenosine for 6 h, after which time media were ...
Here we show that glutamate exocytosis from astrocytes of the rat hippocampal dentate molecular layer enhances synaptic ... Glutamate exocytosis from astrocytes controls synaptic strength Nat Neurosci. 2007 Mar;10(3):331-9. doi: 10.1038/nn1849. Epub ... Here we show that glutamate exocytosis from astrocytes of the rat hippocampal dentate molecular layer enhances synaptic ... pathway is endogenously activated by neuronal activity-dependent stimulation of purinergic P2Y1 receptors on the astrocytes. ...
Astrocytes that were treated with relaxin-2 and relaxin-3 showed a marked decrease in ROS production when compared to control ... Next, to test whether relaxin reduced the production of reactive oxygen species (ROS) astrocytes were exposed to the same ... Mitochondrial membrane potential was higher in astrocytes that were treated with relaxin-2 and relaxin-3 compared to untreated ... Taken together, these data present novel findings that show relaxin protects astrocytes from ischemic conditions through the ...
A single intravascular injection of AAV9 results in widespread transduction of astrocytes in adult mice and of astrocytes and ... In adult mice, tail vein injection of AAV9-GFP leads to robust transduction of astrocytes throughout the entire CNS, with ... through targeting of astrocytes. It may also be useful for rapid postnatal genetic manipulations in basic neuroscience studies. ... Figure 5: Intravenous injection of AAV9 leads to widespread predominant astrocyte transduction in the spinal cord and brain of ...
Astrocytes can be subdivided into fibrous and protoplasmic types. Learn more about astrocytes, including their structure and ... Astrocyte, star-shaped cell that is a type of neuroglia found in the nervous system in both invertebrates and vertebrates. ... Unlike fibrous astrocytes, protoplasmic astrocytes occur in the gray matter of the central nervous system. They have fewer ... Astrocytes divide after injury to the nervous system and occupy the spaces left by injured neurons. Astrocytes also are thought ...
... Yann Bernardinelli, Dominique Muller, and Irina Nikonenko Department of Neuroscience, ... Yann Bernardinelli, Dominique Muller, and Irina Nikonenko, "Astrocyte-Synapse Structural Plasticity," Neural Plasticity, vol. ...
Astrocytes Regulate GLP-1 Receptor-Mediated Effects on Energy Balance David J. Reiner, Elizabeth G. Mietlicki-Baase, Lauren E. ... Dysfunctional Calcium and Glutamate Signaling in Striatal Astrocytes from Huntingtons Disease Model Mice Ruotian Jiang, Blanca ... FGF-1 Triggers Pannexin-1 Hemichannel Opening in Spinal Astrocytes of Rodents and Promotes Inflammatory Responses in Acute ...
During investigations of calcium signaling in astrocytes in living mice, Kuchibhotla et al. discovered a role for astrocytes in ... Thus, while plaques may affect neurons locally, they have a more global effect on the network of astrocytes, hinting to ... In a mouse model of Alzheimers disease, astrocytes respond globally to plaque formation. ... In a mouse model of Alzheimers disease, astrocytes respond globally to plaque formation. ...
Astrocytes respond to a hormone that signals satiety to control synaptic plasticity of neurons that regulate eating. ... Astrocytes respond to a hormone that signals satiety to control synaptic plasticity of neurons that regulate eating. ... Thus, leptin signaling in astrocytes in the region of the brain that controls appetite is necessary for the neuronal response ... created mice with knockout of the leptin receptor in astrocytes of adults and investigated the effects in the hypothalamic ...
... and the connections that the astrocyte makes with other cells of the brain are essential for a variety of important neural ... Astrocytes play diverse roles in central nervous system (CNS) function and dysfunction, ... Astrocytes in Epilepsy; C. Steinhäuser and G. Seifert. Astrocyte Involvement in the Acquired Demyelinating Diseases; S. E. Lutz ... Astrocytes play diverse roles in central nervous system (CNS) function and dysfunction, and the connections that the astrocyte ...
Astrocytes are the main cellular target of CDV and undergo reactive changes already in pre-demyelinating brain lesions. Based ... The aim of the study was to characterize astrocyte plasticity during the course of CDV-induced demyelinating leukoencephalitis ... Gene expression analysis revealed 81 differentially expressed astrocyte-related genes with a dominance of genes associated with ... Observed findings indicate an astrocyte polarization towards a neurotoxic phenotype likely contributing to lesion initiation ...
... fibrous astrocytes »human brain »information processing »interlaminar astrocytes »protoplasmic astrocytes »spinal cord injury » ... fibrous astrocytes , human brain , information processing , interlaminar astrocytes , protoplasmic astrocytes , spinal cord ... Alzheimers »Calcium »Epilepsy »Human astrocytes »astrocytes »blood flow »blood vessel »brain cell »brain function and sensory ... Further reports about: , Alzheimers , Calcium , Epilepsy , Human astrocytes , astrocytes , blood flow , blood vessel , brain ...
Astrocytes respond to injury and disease in the central nervous system (CNS) with a process referred to as reactive astrogl … ... Astrocytes respond to injury and disease in the central nervous system (CNS) with a process referred to as reactive ... It is noteworthy that different stimuli of astrocyte reactivity can lead to similar degrees of GFAP upregulation while causing ... Structural and functional changes are regulated in reactive astrocytes by many different potential signaling events that occur ...
Astrocytes and Vasculature. This laser confocal image shows a GFP transgenic mouse retina under the control of the GFAP ... These labels not only show the spatial relationship of individual astrocytes to one another, but also the vasculature. Image ...
In the present investigation the role of astrocytes and their precursors in guidance of outgrowing corticospinal tract axons in ... Astrocytes and guidance of outgrowing corticospinal tract axons in the rat. An immunocytochemical study using anti-vimentin and ... In the present investigation the role of astrocytes and their precursors in guidance of outgrowing corticospinal tract axons in ... labelling experiments it can be concluded that the vimentin-glial fibrillary acidic protein transition occurs within astrocyte ...
Microglia Give Astrocytes License to Kill 20 Jan 2017. * Purification of Adult Human Astrocytes Shows: They Are Unique 15 Jan ... is associated with similar gene expression changes as seen in reactive astrocytes-the type of astrocytes elicited after brain ... The Aging Astrocyte Transcriptome from Multiple Regions of the Mouse Brain. Cell Rep. 2018 Jan 2;22(1):269-285. PubMed. ... Two studies of astrocytes in aging mouse brain report similar results.. *The cells take on a reactive phenotype, ramping up ...
We are developing new molecular tools to modulate and monitor astrocyte reactivity in situ, in order to disentangle this ... 2. Molecular and functional changes in reactive astrocytes in vivo. Our earlier in vivo studies of reactive astrocytes induced ... 3. Reactive astrocytes as biomarkers for pathological situations Reactive astrocytes appear under pathological conditions, and ... Reactive astrocytes. We study astrocytes, a type of brain glial cells that play key supporting roles for neurons. Under ...
The ATP and NADH produced support metabolism in the astrocyte while the lactate is exported to feed the neuron. Thus, rapid ... In this computational model we show that neuromodulatory stimulation by norepinephrine induces astrocytes to recover glucosyl ... a polymerized form of glucose that is localized largely to astrocytes, but its exact role and conditions of use are not clear. ... wherein glia can provide the ergogenic metabolite lactate to the neuron in a process called the astrocyte-to-neuron shuttle ( ...
Star-shaped cells called astrocytes are much more than simple support cells in the brain. In a new study on mice, researchers ... Tags: Astrocyte, Baby, Blood, Brain, Breathing, Cell, Children, Childrens Health, Fatigue, Fever, Heart, Inflammation, ... Astrocytes were once viewed just as a kind of glue that holds everything in place in the brain. Then they were considered as ... Activation of the astrocytes also caused raised levels of PGE2 and weakened the respiratory centers reaction to high CO2 ...
These cells included endothelial cells and uninfected astrocytes. Remarkably, the infected astrocytes themselves did not ... In NeuroAIDS, Infected Astrocytes May Cause Toxicity, Triggering Apoptosis. Robinson, Richard. Neurology Today: August 04, 2011 ... Astrocytes also play a key role in maintaining the blood-brain barrier. Astrocytic "end feet" surround the blood vessels, ... Home , August 04, 2011 - Volume 11 - Issue 15 , In NeuroAIDS, Infected Astrocytes May Cause Toxicity, Trigge... ...
Therefore, he sees astrocyte conversion working best in combination with other treatments that target the processes driving ... Fu lab postdoc Hao Qian and colleagues expression system glowed red in infected astrocytes, and remained red even if the cells ... Dopaminergic Neurons Conjured from Astrocytes Restore Motion. Go to another part. Series - Joint Keystone Symposia: ... Astrocytes are devoted nurturers of neurons-facilitating synaptic transmission, maintaining the blood-brain barrier, and ...
  • Furthermore, we analyzed whether alpha 1-antichymotrypsin (ACT), which is found in amyloid plaques and can influence A beta fibrillogenesis, affects the A beta uptake by human astrocytes. (lu.se)
  • Thus, primary human astrocytes derived from different sources can bind and internalize A beta 1-42, and fetal astrocytes were more efficient in A beta 1-42 uptake than adult astrocytes. (lu.se)
  • We investigated the cellular response of human-astrocytes and human-CVEC following trauma in vitro. (uwo.ca)
  • On the basis of previous data that showed astrocytes activated with interleukin (IL)-1b induce neuronal injury, we analyzed global gene changes in IL-1b-activated human astrocytes by gene microarray. (elsevier.com)
  • Thus, CD38 expression in HIV-1 and/or IL-1β-stimulated human astrocytes and human brain tissues was analyzed. (elsevier.com)
  • Here, we present the first data that indicates that human astrocytes are capable of expressing ICAM-1 in response to cytokines that either induce or upregulate the expression of DR. In essence, cytokines derived from different cell types seem to exert similar pleiotropic effects on the modulation of MHC and ICAM-1 expression on astrocytes. (ox.ac.uk)
  • Thus, we explored mechanism(s) involved in alcohol-mediated activation of human astrocytes with HIV-1 and subsquent alterations in their inflammatory functions. (unt.edu)
  • With emerging technologies, we have entered a new era of understanding how astrocytes participate in and modulate neuronal activity from the subcellular to mesoscale levels. (frontiersin.org)
  • In particular, we have yet to fully understand: 1) how physiologically and molecularly heterogeneous are astrocytes, 2) how uniform or variable the astrocyte effects are on neurons at various synapses and circuits throughout the CNS, and 3) under what conditions and by what mechanisms do astrocytes modulate neuronal activity? (frontiersin.org)
  • We call for papers (primary research articles, reviews, commentaries, technique reports) on the topic, with an emphasis on the role of astrocytes in neuronal plasticity and in population neuronal activity over time. (frontiersin.org)
  • Astrocytes, a class of non-neuronal cells, have previously been implicated in depression and suicide. (healthcanal.com)
  • Experimental evidence suggests that local impact of astrocytes on single synapses translates into global modulation of neuronal networks and behavior. (harvard.edu)
  • Astrocytes consume the FAs stored in lipid droplets via mitochondrial β-oxidation in response to neuronal activity and turn on a detoxification gene expression program. (meta.org)
  • In vivo astrocytes provide the environment necessary for neuronal function. (uni-potsdam.de)
  • Reactive astrocytes are associated with every form of neurological injury. (jci.org)
  • Because many features of astrocyte development are recapitulated in reactive astrocytes, we investigated the role of nuclear factor I-A (NFIA), a key transcriptional regulator of astrocyte development whose contributions to reactive astrocytes remain undefined. (jci.org)
  • Here, we show that NFIA is highly expressed in reactive astrocytes in human neurological injury and identify unique roles across distinct injury states and regions of the CNS. (jci.org)
  • In the cortex, after ischemic stroke, NFIA is required for the production of reactive astrocytes from the subventricular zone (SVZ). (jci.org)
  • Together, these studies uncover critical roles for NFIA in reactive astrocytes and illustrate how region- and injury-specific factors dictate the spectrum of reactive astrocyte responses. (jci.org)
  • Co-culture models of the BBB typically involve astrocytes seeded on two-dimensional (2D) surfaces, which recent studies indicate cause astrocytes to express a phenotype similar to that of reactive astrocytes in situ. (rti.org)
  • These results demonstrate that astrocyte culture conditions differentially affect their ability to modulate brain endothelial barrier function, and suggest a direct relationship between reactive gliosis and BBB permeability. (rti.org)
  • Here, we use a stringent experimental strategy to molecularly define the astrocyte lineage by integrating microarray datasets across several in vitro model systems of astrocyte differentiation, primary astrocyte cultures, and various astrocyterich CNS structures. (pnas.org)
  • To date, precise genetic analyses of the astrocyte in normal physiology and disease processes have been limited to in vitro studies by using specific glial differentiation model systems ( 10 - 12 ). (pnas.org)
  • De plus, des agonistes cholinergiques ou glutamatergiques qui ont la capacité d'augmenter la concentration de Ca2+ intracellulaire peuvent induire une production du NO in vitro et ex vivo dans les astrocytes, qui est supprimée en présence de l'inhibiteur de NOS non sélectif, L-NG -Nitro-arginine. (umontreal.ca)
  • G ) Schematic overview of in vitro endothelial/astrocyte barrier assay. (jci.org)
  • Based on the emerging roles for astrocytes in neurological disorders, we investigated whether hiPSC-derived astrocyte progenitors could be engrafted to the rodent spinal cord and how the characteristics of these cells changed between in vitro culture and after transplantation to the in vivo spinal cord environment. (broadinstitute.org)
  • In vitro studies confirmed that A beta is taken up by rodent astrocytes, but knowledge on human astrocyte-mediated A beta clearance is sparse. (lu.se)
  • We hypothesized that the culture conditions of astrocytes would differentially affect their ability to modulate BBB function in vitro. (rti.org)
  • This hypothesis is based upon the ability to induce the expression of the class II MHC antigens on astrocytes, and on their ability to present myelin basic protein to encephalitogenic T-cells in vitro. (ox.ac.uk)
  • Brain activity involves essential functional and metabolic interactions between neurons and astrocytes. (umn.edu)
  • Metabolic coordination between neurons and astrocytes is critical for the health of the brain. (meta.org)
  • Together, our findings reveal that FA metabolism between neurons and astrocytes is coupled in an activity-dependent manner to protect neurons from FA toxicity. (meta.org)
  • To explore how astrocytes react to this stimulation, the researchers measured what happened in the visual cortex as they showed mice several visual patterns composed of parallel lines oriented in different directions. (scitechdaily.com)
  • The researchers then did the same test in genetically engineered mice whose astrocytes were disabled. (scitechdaily.com)
  • Fingerprint Dive into the research topics of 'Media components influence viral gene expression assays in human fetal astrocyte cultures. (elsevier.com)
  • Based on the analysis of postmortem brain samples from the Douglas-Bell Canada Brain Bank, it demonstrates that the expression of the astrocyte-specific marker GFAP, which is significantly decreased in the prefrontal cortex of depressed suicides compared to that of healthy controls, is normal in other cortical areas that are not traditionally associated with depression, such as the visual cortex. (healthcanal.com)
  • Astrocytes were viable in 3D conditions, and displayed a marked reduction in their expression of glial fibrillary acidic protein (GFAP), suggesting reduced activation. (rti.org)
  • 3.0.CO;2-X\";s:6:\"\u0000*\u0000pii\";s:0:\"\";s:7:\"\u0000*\u0000pmid\";s:0:\"\";s:9:\"\u0000*\u0000atitle\";s:83:\"Regulation of gelatinases in microglia and astrocyte cell cultures by plant lectins\";s:9:\"\u0000*\u0000jtitle\";s:26:\"Glia (New York, NY. (inist.fr)
  • Our results show that human embryonic stem cell- and hiPSC-derived astrocyte progenitors survive long-term after spinal cord engraftment and differentiate to astrocytes in vivo with few cells from other lineages present. (broadinstitute.org)
  • Gene profiling of the transplanted cells demonstrates the astrocyte progenitors continue to mature in vivo and upregulate a variety of astrocyte-specific genes. (broadinstitute.org)
  • Given this mature astrocyte gene profile, this work highlights hiPSCs as a tool to investigate disease-related astrocyte biology using in vivo disease modeling with significant implications for human neurological diseases currently lacking animal models. (broadinstitute.org)
  • The best in vivo data showing that astrocytes serve as intracerebral APCs is the finding that astrocytes in multiple sclerosis plaques are DR+ (class II MHC in human). (ox.ac.uk)
  • These important efforts have focused on specialized aspects of early glial differentiation and as such have yielded limited information on the diverse roles of astrocytes in normal brain. (pnas.org)
  • Characterization of promoter-proximal THSSs at differentially expressed genes during HD astrocyte differentiation. (biomedcentral.com)
  • a Venn diagram showing overlap of genes differentially expressed between HD and WT cells at each stage of astrocyte differentiation. (biomedcentral.com)
  • In this study, we have defined the mature astrocyte on the molecular level through an exhaustive and integrated transcriptional analysis of many distinct astrocyte-rich cultures and CNS tissues by using standard and nonstandard bioinformatic approaches. (pnas.org)
  • Stimulation of astrocytes with transforming growth factor (TGF)beta1 decreased transendothelial electrical resistance (TEER) and reduced expression of claudin-5 in co-cultures, whereas treatment of endothelial cells in the absence of astrocytes was without effect. (rti.org)
  • Medium collected from astrocyte cultures during (but not before) calcium wave stimulation contains ATP. (elsevier.com)
  • Media components influence viral gene expression assays in human fetal astrocyte cultures. (elsevier.com)
  • We have developed highly enriched astrocyte cultures for neurovirological study by culturing in a serum-free defined medium, B16, supplemented with basic fibroblast growth factor (FGF-2). (elsevier.com)
  • By comparison, CNS cultures developed in standard serum-containing medium initially contain predominantly astrocytes, but show increasing contamination with fibroblasts with sequential passage. (elsevier.com)
  • These cultures support CMV viral synthesis in both fibroblasts and astrocytes, cell types distinguishable only by immunostaining for cell specific antigen. (elsevier.com)
  • We used the pH-sensitive fluorescent dye BCECF to study intracellular pH (pH i ) regulation in primary cultures of rat astrocytes and C6 glioma cells. (wright.edu)
  • This global perspective in the normal brain also provides a framework for how astrocytes may participate in the pathogenesis of common neurological disorders like Alzheimer's disease, Parkinson's disease, stroke, epilepsy, and primary brain tumors. (pnas.org)
  • In the brain, astrocytes are the most abundant glial cells and play various roles including maintenance of tripartite synapses and regulation of CBF. (umontreal.ca)
  • We are keen to receive submissions on astrocyte functions pertaining to circuits in specific physiological systems towards the overall goal of highlighting shared principles and heterogeneity of astrocyte-neuron interactions across different brain regions. (frontiersin.org)
  • In the spinal cord, after white matter injury (WMI), NFIA-deficient astrocytes exhibit defects in blood-brain barrier remodeling, which are correlated with the suppression of timely remyelination. (jci.org)
  • This research provides evidence that networks of astrocytes are altered specifically in areas of the brain associated with mood regulation. (healthcanal.com)
  • In addition, in describing the existence of new subtypes of astrocyte, this study reveals features specific to the human brain. (healthcanal.com)
  • The diversity and functional and morphological complexity of cortical astrocytes in humans, as well as their involvement in normal and pathological brain function, have only recently begun to be recognized. (healthcanal.com)
  • Integrated within neural circuits, astrocytes have recently been shown to modulate brain rhythms thought to mediate sleep function. (harvard.edu)
  • When the brain is attentive, those cells, called astrocytes, relay messages alerting neurons of the visual cortex that they should respond strongly to whatever visual information they are receiving. (scitechdaily.com)
  • In this study, the researchers focused on what astrocytes do when the brain is stimulated to pay attention to a specific visual stimulus. (scitechdaily.com)
  • These cell types - astrocytes, inhibitory neurons - are emerging as major players in brain disorders, in unexpected ways. (scitechdaily.com)
  • Blood-brain barrier (BBB) function is regulated by dynamic interactions among cell types within the neurovascular unit, including astrocytes and endothelial cells. (rti.org)
  • Brain endothelial cells were grown alone or in co-culture with astrocytes. (rti.org)
  • Astrocytes are commonly thought to be primarily involved in transmitter glutamate cycling, a mechanism that however only accounts for few % of brain energy utilization. (umn.edu)
  • Our results emphasize the importance of K + in stimulating the activation of astrocytes, which is relevant to the understanding of brain activity and energy metabolism at the cellular level. (umn.edu)
  • Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. (meta.org)
  • It has been suggested that the brain astrocyte can function as a facultative antigen presenting cell (APC). (ox.ac.uk)
  • If astrocytes function as immunocompetent APCs within the brain, it would seem that they would also be able to express molecules important for intercellular adhesion. (ox.ac.uk)
  • For instance, astrocytes may express voltage-gated ion channels and neurotransmitter receptors that are coactivated at synapses and then participate in removing potentially toxic excitatory amino acids from synapses by high-affinity transporters ( 7 ). (pnas.org)
  • Dans le cerveau, les astrocytes sont les cellules gliales les plus abondantes et elles jouent divers rôles, y compris le maintien des synapses tripartites et la régulation du débit sanguin cérébral (DSC). (umontreal.ca)
  • However, how EtOH regulates HIV-1-induced astrocyte neuroinflammation is unknown. (unt.edu)
  • This perceived limited functional range of the astrocyte is not consistent with the emerging data that they may retain stem cell-like properties ( 3 , 4 ) and modulate almost every facet of functional neural networks ( 5 , 6 ). (pnas.org)
  • The findings, published this week in the online edition of the Proceedings of the National Academy of Sciences , are the latest in a growing body of evidence suggesting that astrocytes are critically important for processing sensory information, says Mriganka Sur, the Paul E. and Lilah Newton Professor of Neuroscience at MIT and senior author of the paper. (scitechdaily.com)
  • More directly than any other study to date, it illustrates the critical role of astrocytes in plasticity," says Michael Merzenich, a professor emeritus of neuroscience at the University of California at San Francisco, who was not part of the research team. (scitechdaily.com)
  • H ) NFIA-deficient astrocytes exhibited decreased TEER electrical resistance when cocultured with endothelial cells. (jci.org)
  • The effect of TGFbeta1 on TEER was significantly more pronounced in endothelial cells cultured with 3D astrocytes compared to 2D astrocytes. (rti.org)
  • The lumen of the BBB is lined with cerebrovascular endothelial cells (CVEC) that are ensheathed with perivascular astrocyte endfeet. (uwo.ca)
  • The vertebrate CNS is comprised of three predominant cell types (neurons, oligodendrocytes, and astrocytes) that are thought to arise from multipotent neural stem cells (NSCs). (pnas.org)
  • However, neuron-astrocyte coupling of lipid metabolism, particularly in response to neural activity, remains largely uncharacterized. (meta.org)
  • The intersection of astrocyte data sets, coupled with the application of nonastrocytic exclusion filters, yielded many astrocyte-specific genes possessing strikingly varied patterns of regional CNS expression. (pnas.org)
  • Annotation of these astrocyte-specific genes provides direct molecular documentation of the diverse physiological roles of the astrocyte lineage. (pnas.org)
  • The resulting astrocyte-specific candidate genes were subjected to a rigorous RNA in situ hybridization (ISH) validation scheme that revealed distinctive regional patterns of expression. (pnas.org)
  • CI induces astrocyte monolayer retraction and activation, with predominant phosphorylation of JNK1/2 MAPK. (uwo.ca)
  • These results suggest an important role of CD38 in the regulation of astrocyte dysfunction during the neuroinflammatory processes involved in neurodegenerative/neuroinflammatory disorders such as HIV-1 encephalitis. (elsevier.com)
  • Therefore, by means of flow cytometry and confocal laser scanning microscopy (CLSM), we evaluated the binding and internalization of A beta 1-42 by primary human fetal astrocytes and adult astrocytes, isolated from nondemented subjects (n = 8) and AD subjects (n = 6). (lu.se)
  • The induction of intercellular adhesion molecule 1 (ICAM-1) expression on human fetal astrocytes by interferon-gamma, tumor necrosis factor alpha, lymphotoxin, and interleukin-1: relevance to intracerebral antigen presentation. (ox.ac.uk)
  • In summary, our results demonstrate that EtOH-mediated astrocyte inflammation and cytotoxicity in context of HAND occurs via cPLA 2 signaling. (unt.edu)
  • a APOE mRNA expression relative to Gapdh and 18S mRNA contents in APOE3 and APOE4 immortalized astrocytes, quantified by real time qPCR ( N = 3). (biomedcentral.com)
  • IL-1β and HIV-1 activation of astrocytes enhanced CD38 mRNA levels. (elsevier.com)
  • Astrocyte involvement in neuron homeostasis may also extend to trophic support ( 8 ), antioxidant functions, and production of critical substrates for neuron membrane synthesis. (pnas.org)
  • To this end, we took into account ion pumps and voltage/ligand-gated channels using the stoichiometry derived from available energy budget for neocortical signaling and incorporated this stoichiometric relation into a computational metabolic model of neuron-astrocyte interactions. (umn.edu)
  • The astrocyte represents the most abundant yet least understood cell type of the CNS. (pnas.org)
  • Although they have been thought for a long time to require gap junctions, we recently demonstrated that mouse cortical astrocytes use an extracellular messenger for calcium wave propagation. (elsevier.com)
  • We found that astrocytes are stimulated by the extracellular K + exiting neurons in excess of the 3/2 Na + /K + ratio underlying Na + /K + ATPase-catalyzed reaction. (umn.edu)
  • These findings indicate that CI elicits differential BBB cell responses: JNK-mediated astrocyte retraction and CVEC-dependent increase in leukocyte recruitment, the phenomena that may contribute to overall BBB dysfunction following TBI. (uwo.ca)
  • c Representative traces and quantification of the magnitude of ATP-induced Ca 2+ responses in APOE3 astrocytes transfected with lipofectamine (lipo), plus scramble (sc) or APOE siRNA, and APOE4 astrocytes treated only with lipofectamine ( N = 4). (biomedcentral.com)
  • f Quantification of the magnitude of Ca 2+ responses elicited by 100 μM ATP in APOE3 astrocytes transfected with GFP or GFP- APOE4 plasmids, as indicated. (biomedcentral.com)
  • Alcohol exposure altered the morphology of astrocytes, proinflammatory responses and induced cytotoxicity in a dose-dependent manner. (unt.edu)
  • In a follow-up study, the researchers are planning to study how astrocytes are affected in mouse models of Alzheimer's. (scitechdaily.com)
  • CD38 knockdown using specific siRNAs significantly reduced astrocyte proinflammatory cytokine and chemokine production. (elsevier.com)
  • Historically, astrocytes have been viewed as a homogenous population of cells functioning to provide passive support by supply of essential substrates and removal of toxic metabolites. (pnas.org)
  • Astrocytes are largest class of glial cells, and are morphologically and physiologically adapted to play an integral part of central nervous system (CNS) activity. (frontiersin.org)
  • A - D ) Deletion of NFIA from astrocytes resulted in an increase in the presence of albumin ( A versus C ) and a decrease in the expression of the astrocyte endfeet protein Aqp4 ( B versus D .) Graphs in E and F are derived from 4 animals per genotype, and quantification involved 8 sections per animal. (jci.org)