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*  Live Imaging of Neuroinflammation Reveals Sex and Estrogen Effects on Astrocyte Response to Ischemic Injury | Stroke
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 ...
http://stroke.ahajournals.org/content/39/3/935
*  Binding and Uptake of A beta 1-42 by Primary Human Astrocytes In Vitro
article{9714ffdf-1e21-475d-ac0b-daebdc2182ca, abstract = {Clearance of the amyloid-P peptide (A beta) as a remedy for Alzheimer's 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 ...
https://lup.lub.lu.se/search/publication/1443637
*  The impact of defective gp130/SOCS3 signaling on the astrocyte response to hyper-IL6 (38.17) | The Journal of Immunology
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 ...
http://www.jimmunol.org/content/182/1_Supplement/38.17
*  Interactions between Sirt1 and MAPKs regulate astrocyte activation induced by brain injury in vitro and in vivo | Journal of...
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 ...
https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-017-0841-6
*  Laminins containing the β2 and γ3 chains regulate astrocyte migration and angiogenesis in the retina | Development
An astrocyte-derived template is crucial for the development of retinal angiogenesis (Dorrell et al., 2002; Uemura et al., 2006). In adults, astrocytes play a crucial role in maintaining the blood-retinal barrier (BRB). To date, the factors that guide astrocytes into the retina are not well characterized. However, astrocytes isolated from the rat brain migrate towards laminin (Armstrong et al., 1990), suggesting a possible role for laminins in inducing astrocyte migration. In this study, using both in vivo and in vitro assays, we provide evidence that laminins at the ILM regulate astrocyte migration, spatial organization and subsequent vascular growth.. In the retina, laminins are crucial for ILM formation (Pinzón-Duarte et al., 2010; Hirrlinger et al., 2011; Halfter et al., 2005; Edwards et al., 2010). Similarly, mutations in α-dystroglycan (a laminin receptor) and in an enzyme that participates in glycosylation of α-dystroglycan (POMGnT1) also produce ...
http://dev.biologists.org/content/140/9/2050
*  Heterogeneity in astrocyte responses after acute injury in vitro and in vivo
Astrocytes present a major population of glial cells in the adult mammalian brain. The heterogeneity of astrocytes in different regions of the healthy central nervous system (CNS) and their physiological functions are well understood. In contrast, rather little is known about the diversity of astrocyte reactions under pathological conditions. After CNS injury the reaction of astrocytes, also termed 'reactive astrogliosis', is characterized by morphological and molecular changes such as hypertrophy, polarization, migration and up-regulation of intermediate filaments. So far, it was unknown whether all astrocytes undergo these changes, or whether only specific subpopulations of reactive astrocytes possess special plasticity. Since some quiescent, postmitotic astrocytes in the cortical gray matter apparently de-differentiate and re-enter the cell cycle upon injury, reactive astrocytes have the ...
https://edoc.ub.uni-muenchen.de/16152/index.html
*  Astrocytes at Single Synapses | Science Signaling
Astrocytes respond to synaptic activity and can release different gliotransmitters, which modulate neuronal activity and neurotransmission. Perea and Araque examined the role of astrocytes on synaptic transmission at single hippocampal excitatory synapses. Ca2+ elevation in astrocytes led to a transient release of the neurotransmitter glutamate from astrocytes, which was mediated by metabotropic glutamate receptors. Potentiation became long-lasting when glial activation was paired with postsynaptic depolarization.. G. Perea, A. Araque, Astrocytes potentiate transmitter release at single hippocampal synapses. Science 317, 1083-1086 (2007). [Abstract] [Full Text]. ...
http://stke.sciencemag.org/content/2007/401/tw313
*  The induction of intercellular adhesion molecule 1 (ICAM-1) expression on human fetal astrocytes by interferon-gamma, tumor...
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 ...
https://www.ndorms.ox.ac.uk/publications/482693
*  Glial-derived proteins activate cultured astrocytes and enhance beta amyloid-induced glial activation.
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 ...
http://www.prohealth.com/library/showarticle.cfm?libid=1723
*  Characterisation of the Expression of NMDA Receptors in Human Astrocytes
Astrocytes have long been perceived only as structural and supporting cells within the central nervous system (CNS). However, the discovery that these glial cells may potentially express receptors capable of responding to endogenous neurotransmitters has resulted in the need to reassess astrocytic physiology. The aim of the current study was to characterise the expression of NMDA receptors (NMDARs) in primary human astrocytes, and investigate their response to physiological and excitotoxic concentrations of the known endogenous NMDAR agonists, glutamate and quinolinic acid (QUIN). Primary cultures of human astrocytes were used to examine expression of these receptors at the mRNA level using RT-PCR and qPCR, and at the protein level using immunocytochemistry. The functionality role of the receptors was assessed using intracellular calcium influx experiments and measuring extracellular lactate dehydrogenase (LDH) activity in primary cultures of human ...
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0014123
*  Monitoring reactive gliosis in 3-dimensional astrocyte cultures; a model of spinal cord damage - Open Research Online
Primary rat astrocytes maintained in 3-dimensional (3D) type-1 collagen gels showed a significantly lower level of reactivity than 2D cultures as determined by immunofluorescence detection of GFAP, vimentin, aquaporin-4, CSPGs and S100β. The 3D cells were therefore reminiscent of astrocytes in the undamaged CNS, and could be used as a baseline for investigating induction and progression of reactive gliosis. In order to verify this system as a useful model, 3D astrocyte cultures were either stimulated continually with TGFβ1 or maintained in control media for 15 days. Immunofluorescence detection and image analysis were used to quantify changes in GFAP, vimentin, aquaporin-4 and CSPG in response to TGFβ1-stimulation. There was a clear increase in detection of this panel of reactivity markers with time in culture in the astrocytes exposed to TGFβ1 whilst control cultures showed little change. For further validation of this system as a useful model that permits ...
http://oro.open.ac.uk/12840/
*  Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1)-facilitated HIV restriction in astrocytes...
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 ...
https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-015-0285-9
*  A crucial role for Olig2 in white matter astrocyte development | Development
When D'Arcy Wentworth Thompson's 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 D'Arcy Thompson's work and an overview of the articles in this issue.. ...
http://dev.biologists.org/content/early/2007/04/11/dev.02847
*  Meteorin: a secreted protein that regulates glial cell differentiation and promotes axonal extension | The EMBO Journal
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 ...
http://emboj.embopress.org/content/23/9/1998
*  Astrocytes Give Rise to New Neurons in the Adult Mammalian Hippocampus | Journal of Neuroscience
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 ...
http://www.jneurosci.org/content/21/18/7153.long
*  Effects of tenascin-C in cultured hippocampal astrocytes: NCAM and fibronectin immunoreactivity changes.
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 ...
http://www.hal.inserm.fr/inserm-00522473
*  Transplantation of Specific Human Astrocytes Promotes Functional Recovery after Spinal Cord Injury
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 ...
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017328
*  北京大学医学部机构知识库(IR@PKUHSC): The association of 14-3-3 gamma and actin plays a role in cell division and apoptosis in astrocytes
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 ...
http://ir.bjmu.edu.cn/handle/400002259/67757
*  A model for glioma cell migration on collagen and astrocytes | Journal of The Royal Society Interface
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 ...
http://rsif.royalsocietypublishing.org/content/5/18/75
*  Plus it
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 ...
http://www.jneurosci.org/content/31/23/8342
*  Metallothionein-3 modulates the amyloid β endocytosis of astrocytes through its effects on actin polymerization | Molecular...
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 ...
https://molecularbrain.biomedcentral.com/articles/10.1186/s13041-015-0173-3
*  Electrophysiological behavior of neonatal astrocytes in hippocampal stratum radiatum | Molecular Brain | Full Text
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 ...
https://molecularbrain.biomedcentral.com/articles/10.1186/s13041-016-0213-7
*  A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse | Science
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. ...
http://science.sciencemag.org/content/346/6206/237
*  Loss of Astrocyte Polarization in the Tg-ArcSwe Mouse Model of Alzheimer's Disease
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 Alzheimer's 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 ...
http://uu.diva-portal.org/smash/record.jsf?pid=diva2:471282
*  How might brain "astrocytes" alter nerve cell connections and contribute to Autism Spectrum Disorder?
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 Rett's 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. ...
http://www.dana.org/Media/GrantsDetails.aspx?id=123059