Disappeared from immature oligodendrocytes (Fig. 7). The peak of OPC proliferation in cerebellum is around P4, and the number of OPCs increases until P7 .
This protocol generates oligodendrocyte progenitor cells from human pluripotent stem cells. The cells can subsequently be isolated by cell sorting for myelination studies, or they can be terminally differentiated to MBP+ oligodendrocytes. In the CNS, oligodendrocytes act as the myelinating cells. Oligodendrocytes have been identified to be key players in several neurodegenerative disorders. This protocol describes a robust, fast and reproducible differentiation protocol to generate human oligodendrocytes from pluripotent stem cells (PSCs) using a chemically defined, growth factor-rich medium. Within 8 d, PSCs differentiate into paired box 6-positive (PAX6+) neural stem cells, which give rise to OLIG2+ progenitors by day 12. Oligodendrocyte lineage transcription factor 2-positive (OLIG2+) cells begin to express the transcription factor NKX2.2 around day 18, followed by SRY-box 10 (SOX10) around day 40. Oligodendrocyte progenitor cells (OPCs) that are positive for the cell surface antigen recognized by
We demonstrate that neonatal hypoxia causes transient hypomyelination due to significantly increased oligodendrocyte cell death and delayed oligodendrocyte differentiation. One week after hypoxia, the main populations affected comprised CC1+ mature oligodendrocytes, which are normally involved in myelination. The reduction in mature oligodendrocytes decreased the expression of myelin proteins, likely as a result of both oligodendrocyte death and delayed oligodendrocyte maturation. Previous studies have shown that oligodendrocyte depletion after hypoxia-ischemia is caused by degeneration of O4+ preoligodendrocytes and by arrested oligodendrocyte maturation at a premyelinating developmental stage (Ness et al., 2001; Back et al., 2002). Our study demonstrates an increased number of Caspase-3+ oligodendrocytes the first week after hypoxic insult, but this was not sustained for a longer period after hypoxia. This finding is consistent with the recovery of myelin protein levels a week after ...
MicroRNAs (miRNAs) are important for the regulation of various processes in cell biology. However, the function of miRNAs in the central nervous system and especially in glial cells is still poorly understood. Oligodendroglial cells in the CNS are required for the myelination of the axonal tracts. At initial stages of CNS development and maturation, cells of the oligodendroglial lineage are produced in great excess to ensure sufficient myelination of the CNS. Specific gene regulation programs are required for proliferation, differentiation and apoptosis of oligodendrocytes. We determined whether miRNAs are participating in these processes by regulating important developmental genes. We generated oligodendrocyte-specific Dicer knock-out mutant mice to show the general impact of miRNAs on oligodendrocytes in vivo. The depletion of mature miRNAs resulted in a decreased oligodendrocyte cell number. Microarray profiling of primary oligodendrocytes revealed that the miR-17~92 family of miRNA cluster ...
Anti-myelin immunity is commonly thought to drive multiple sclerosis, yet the initial trigger of this autoreactivity remains elusive. One of the proposed factors for initiating this disease is the primary death of oligodendrocytes. To specifically test such oligodendrocyte death as a trigger for anti-CNS immunity, we inducibly killed oligodendrocytes in an in vivo mouse model. Strong microglia-macrophage activation followed oligodendrocyte death, and myelin components in draining lymph nodes made CNS antigens available to lymphocytes (white blood cells) . However, even conditions favoring autoimmunity-bystander activation, removal of regulatory T cells, presence of myelin-reactive T cells and application of demyelinating antibodies-did not result in the development of CNS inflammation after oligodendrocyte death. In addition, this lack of reactivity was not mediated by enhanced myelin-specific tolerance. Thus, in contrast with previously reported impairments of oligodendrocyte physiology, ...
RESULTS: Three subsets of putative OPCs were identified in adult brains: (1) A2B5(+), (2) O4(low), and (3) A2B5(+)O4(high) MOG(+) progenitors. In comparison, foetal brains contained (1) A2B5(+), (2) O4(+), and (3) A2B5(+)O4(+) progenitors, but no MOG(+) cells. We demonstrate that like fetal OPCs, adult OPCs have the capacity to ensheathe cerebellar axons. However, adult OPCs exhibit low to undetectable expression of miRNAs that were highly expressed in O4-expressing foetal OPCs. Adult OPCs also express different miRNAs compared to mature oligodendrocytes ...
In the adult brain, multipotent progenitor cells have been identified in three areas: the ventricular-subventricular zone (VZ-SVZ), adjacent to the striatal wall of the lateral ventricles, the subgranular zone (SGZ), located at the dentate gyrus of the hippocampus and the subcallosal zone (SCZ), located between the corpus callosum and the CA1 and CA2 regions of the hippocampus. The neural progenitor cells of these regions express the epidermal growth factor receptor (EGFR, ErbB-1 or HER1). EGF, the most important ligand for the EGFR, is a potent mitogenic agent that stimulates proliferation, survival, migration and differentiation into the oligodendrocyte lineage. Other ErbB receptors also activate several intracellular pathways for oligodendrocyte specification, migration and survival. However the specific downstream pathways related to oligodendrogenesis and the hierarchic interaction among intracellular signaling cascades is not well-known. We summarize the current data regarding the role of
TY - JOUR. T1 - TPO1, a member of a novel protein family, is developmentally regulated in cultured oligodendrocytes. AU - Krueger, W. H.H.. AU - Gonye, G. E.. AU - Madison, D. L.. AU - Murray, K. E.. AU - Kumar, M.. AU - Spoerel, N.. AU - Pfeiffer, S. E.. PY - 1997/10. Y1 - 1997/10. N2 - Although the myelin membrane contains only a small set of major proteins more sensitive assays indicate the presence of a plethora of uncharacterized proteins. We have used an antibody perturbation approach to reversibly block the differentiation of prooligodendroblasts into myelinating cells, and, in combination with a differential screening procedure, identified novel mRNAs that are activated during this period. One cDNA, TPO1, recognizes a 5.5-kb mRNA that is strongly up-regulated in oligodendrocytes after release of the differentiation block and that is expressed at high levels in brain tissue during active myelination. This cDNA represents at least two mRNAs differing from each other in their 5-termini. ...
Proteolipid protein (PLP) is the most abundant transmembrane protein in myelin of the central nervous system. Conflicting models of PLP topology have been generated by computer predictions based on its primary sequence and experiments with purified myelin. We have examined the initial events in myelin synthesis, including the insertion and orientation of PLP in the plasma membrane, in rat oligodendrocytes which express PLP and the other myelin-specific proteins when cultured without neurons (Dubois-Dalcq, M., T. Behar, L. Hudson, and R. A. Lazzarini. 1986. J. Cell Biol. 102:384-392). These cells, identified by the presence of surface galactocerebroside, the major myelin glycolipid, were stained with six anti-peptide antibodies directed against hydrophilic or short hydrophobic sequences of PLP. Five of these anti-peptide antibodies specifically stained living oligodendrocytes. Staining was only seen approximately 10 d after PLP was first detected in the cytoplasm of fixed and permeabilized cells, ...
The present study identifies cAMP‐Erk1/2/p38Mapk‐Creb1 signalling as a functionally important intracellular signalling cascade for CNS remyelination that is regulated at the earliest stages of OPC differentiation. These data complement previous studies demonstrating a role for Erk2 and p38Mapk (Chew et al, 2010) as positive regulators of oligodendrocyte differentiation in vitro and during developmental myelination. Loss of ERK2 attenuates OPC differentiation and leads to a delay but not a complete arrest in the appearance of differentiated oligodendrocytes in vivo (Fyffe‐Maricich et al, 2011). Similarly, p38Mapk inhibition decreases OPC differentiation and Mbp expression without effecting either proliferation or survival (Chew et al, 2010). Reporter assay studies have demonstrated that p38MAPK activity up‐regulates the activity and/or expression of transcription factors that can bind the 2 kb mouse MBP promoter. However, p38MAPK can also antagonize ERK, JNK, c‐Jun phosphorylation. We ...
The P2Y-like receptor GPR17 is a G protein-coupled receptor activated by uracil nucleotides and cysteinyl-leukotrienes (Ciana et al., 2006. EMBO J. 25:4615-27). We have previously demonstrated that GPR17 is a key regulator of oligodendroglial differentiation. Under physiological conditions, the receptor starts to be expressed in oligodendrocyte precursor cells (OPCs) also positive for the early marker NG2, it reaches a peak of expression in immature oligodendrocytes, and it is progressively downregulated during terminal maturation (Lecca et al., 2008. PLoS One. 3:e3579; Fumagalli et al., 2011. J Biol Chem. 286:10593-604). At early differentiation stages, activation of GPR17 with agonists induced, while inhibition with antagonists or specific interfering RNAs impaired OPC maturation. At later stages, the forced overexpression of the receptor also led to impaired maturation. All these data suggest that the expression of the receptor GPR17 needs to be time regulated either at transcriptional, or ...
Multiple sclerosis involves an aberrant autoimmune response and progressive failure of remyelination in the central nervous system. Prevention of neural degeneration and subsequent disability requires remyelination through the generation of new oligodendrocytes, but current treatments exclusively target the immune system. Oligodendrocyte progenitor cells are stem cells in the central nervous system and the principal source of myelinating oligodendrocytes. These cells are abundant in demyelinated regions of patients with multiple sclerosis, yet fail to differentiate, thereby representing a cellular target for pharmacological intervention. To discover therapeutic compounds for enhancing myelination from endogenous oligodendrocyte progenitor cells, we screened a library of bioactive small molecules on mouse pluripotent epiblast stem-cell-derived oligodendrocyte progenitor cells. Here we show seven drugs function at nanomolar doses selectively to enhance the generation of mature oligodendrocytes ...
Here we document protocols for the production, isolation, and maintenance of the oligodendrocyte phenotype from rodent and human neural stem cells. Our unique method relies on a series of chemically defined media, specifically designed and carefully characterized for each developmental stage of oligodendrocytes as they advance from oligodendrocyte progenitors to mature, myelinating oligodendrocytes.
Myelin loss is frequently observed in human Alzheimers disease (AD) and may constitute to AD-related cognitive decline. A potential source to repair myelin defects are the oligodendrocyte progenitor cells (OPCs) present in an adult brain. However, until now, little is known about the reaction of these cells toward amyloid plaque deposition neither in human AD patients nor in the appropriate mouse models. Therefore, we analyzed cells of the oligodendrocyte lineage in a mouse model with chronic plaque deposition (APPPS1 mice) and samples from human patients. In APPPS1 mice defects in myelin integrity and myelin amount were prevalent at 6 months of age but normalized to control levels in 9-month-old mice. Concomitantly, we observed an increase in the proliferation and differentiation of OPCs in the APPPS1 mice at this specific time window (6-8 months) implying that improvements in myelin aberrations may result from repair mechanisms mediated by OPCs. However, while we observed a higher number of ...
View Human/Mouse/Rat/Chicken Oligodendrocyte Marker O1 Antibody O1 (MAB1327) datasheet. Validated in CyTOF-ready, Flow, ICC/IF
Primary cell cultures: human fetal material, oligodendrocyte isolation, enrichment, and maturation. Human fetal spinal cord tissue was obtained from the Einstein Human Fetal Tissue Repository (New York, NY) as approved by the Institutional Review Board. Tissues from abortuses of normal women were collected after elective pregnancy termination. Informed consent was obtained from all tissue donors. The ages of the abortuses were determined by multiple parameters, including the date of the last menstrual period by history, uterine size by bimanual and abdominal examination, ultrasonography by using predominantly the maximum biparietal diameter, and, postabortally, by measurement of fetal foot length (Streeter, 1920; Hern, 1984). After retrieval of tissue the spinal cords were stored in sterile medium with antibiotics on ice and were obtained from the neuropathologist within the hour. For cultures the oligodendrocytes were obtained from 21-23 gestational weeks (gw) human fetal spinal cords. The ...
Remyelination is a critical repair process in demyelinating diseases such as multiple sclerosis (MS). Chondroitin sulfate proteoglycans (CSPGs), a family of large molecules consisting of a core protein and glycosaminoglycans comsposed of chains of alternating sugars, are enriched in glial scars. In MS lesions, CSPGs accumulate as constituents of demyelinating plaques, which inhibit the migration and differentiation of oligodendrocyte precursor cells and remyelination.. The research group of Researcher Akihiro Fujikawa and Professor Masaharu Noda of the National Institute for Basic Biology (NIBB) developed a screening method to obtain neutralizing agents for canceling the inhibitory effects of CSPGs on oligodendrocyte differentiation. The group found that the inhibitory activity of a representative extracellular matrix CSPG molecule, aggrecan, was neutralized by a polycationic peptide, protamine, that is clinically used to stop the anticoagulant effect of heparin.. They also found that protamine ...
Nerve conduction within the mammalian central nervous system is made efficient by oligodendrocyte-derived myelin. Historically, thyroid hormones have a well described role in regulating oligodendrocyte differentiation and myelination during development; however, it remains unclear which thyroid hormone receptors are required to drive these effects. This is a question with clinical relevance since nonspecific thyroid receptor stimulation can produce deleterious side-effects. Here we report that GC-1, a thyromimetic with selective thyroid receptor β action and a potentially limited side-effect profile, promotes in vitro oligodendrogenesis from both rodent and human oligodendrocyte progenitor cells. In addition, we used in vivo genetic fate tracing of oligodendrocyte progenitor cells via PDGFαR-CreER;Rosa26-eYFP double-transgenic mice to examine the effect of GC-1 on cellular fate and find that treatment with GC-1 during developmental myelination promotes oligodendrogenesis within the corpus ...
Background Transplantation of oligodendrocyte precursor cells (OPCs) is an attractive therapy for demyelinating illnesses. cable lesion quantity along with boost in able to escape neurons and myelin were present compared to the control group. Such histological improvement related well with an boost in behavioral recovery. Further research recommended that buy 50-91-9 CsA treatment could slow down infiltration of Testosterone levels cells and account activation of citizen microglia and/or macrophages made from infiltrating monocytes in harmed vertebral wires, which contributes to the survival of engrafted repair and OPCs of vertebral cord injury (SCI). A conclusion These outcomes jointly suggest that CsA can promote the success of engrafted OPCs in harmed vertebral wires, but provides no impact on their difference. The engrafted cells differentiated into astrocytes mainly, but not really oligodendrocytes. The helpful impact of CsA on SCI and the success of engrafted cells may end up being ...
Dont let the name fool you. Theres nothing minor about microRNAs. In one fell swoop, a single one can modulate the synthesis of tens, or perhaps hundreds, of proteins. Is it any wonder that these newest members of the RNA family have turned out to be master regulators of basic biology? If you still need convincing, check out the back-to-back microRNA (miRNA) papers in yesterdays Neuron. Working independently, two research groups have discovered why oligodendrocyte precursor cells suddenly stop proliferating and start producing myelin. The answer is an miRNA switch that simultaneously turns off proliferation and turns on maturation. The findings not only show the power that a few miRNAs can wield, but it also may help scientists better understand why oligodendrocytes sometimes go awry, as in gliomas and bouts of demyelination, which can occur in Alzheimer disease.. During development, oligodendrocyte precursor cells (OPCs) rapidly migrate and expand into white matter tracts in the central ...
en] Oligodendrocyte precursor (OP) cells are exposed to multiple extrinsic signals that control their proliferation and differentiation. Previous cell proliferation studies and electrophysiological analysis in cultured cells and in brain slices have suggested that outward potassium channels, particularly Kv1 subunits, may have a prominent role in OP cell proliferation. In the present study, we assessed to what extent overexpression of Kv1.3, Kv1.4, Kv1.5, and Kv1.6 can affect OP cell proliferation and differentiation in culture. We observed that overexpression of Kv1.3 or Kv1.4 increased OP cell proliferation in the absence of mitogens, whereas Kv1.6 overexpression inhibited mitogen-induced OP cell cycle progression. Interestingly, Kv1.3, Kv1.4, Kv1.5, and Kv1.6 overexpression did not interfere with the kinetics of oligodendrocyte differentiation. This study represents the first demonstration that the activity of potassium channels containing distinct Kv1 subunit proteins directly controls ...
We have shown that thyroid hormone regulates the timely expression of the major myelin proteins (MAG,PLP,MBP) during rat brain development. In order to know if this effect is due to changes in the population of oligodendrocytes, we have been studying oligodendrocyte generation in vitro to obtain insights into how the timely generation of these cells might be regulated and the role of thyroid hormone (T3) in this process. T3 effects on the oligoedendrocyte lineage are: decrease of the proliferation rate of the OPCs, promotion of the oligodendrocyte differentiation and increase of the oligodendrocyte maturation.. ...
Myelinating oligodendrocytes arise from migratory and proliferative oligodendrocyte progenitor cells (OPCs). Complete myelination requires that oligodendrocytes be uniformly distributed and form numerous, periodically spaced membrane sheaths along the entire length of target axons. Mechanisms that d …
Oligodendrocytes are the myelinating cells of the CNS and, like neurons, are highly sensitive to ischemic damage. However, the mechanisms underlying cytotoxicity in oligodendrocytes during hypoxic/ischemic episodes are not fully understood. TASK-1 is a K(+) leak channel that mediates hypoxic depolarisation in neurons. The expression and function of TASK-1 in oligodendrocytes had not previously been addressed. In this study, we investigate the expression of TASK-1 in oligodendrocytes and its role in white matter ischemic damage. Expression of TASK-1 in oligodendrocytes was investigated in the mouse brain using immunostaining. TASK-1 channel function was identified by established pharmacological and electrophysiological strategies, using the whole-cell patch clamp technique in cell cultures of oligodendrocytes from the optic nerve, a typical white matter tract. The role of TASK-1 in hypoxia was examined in isolated intact optic nerves subjected to oxygen glucose deprivation (OGD). Oligodendrocytes ...
Oligodendrocyte precursor cells (OPCs) constitute the main proliferative cells in the adult brain, and deregulation of OPC proliferation-differentiation balance results in either glioma formation or defective adaptive (re)myelination. OPC differentiation requires significant genetic reprogramming implicating chromatin remodeling. Mounting evidence indicates that chromatin remodelers play important roles during normal development and their mutations are associated with neurodevelopmental defects, with CHD7 haploinsuficiency being the cause of CHARGE syndrome and CHD8 being one of the strongest Autism Spectrum Disorder (ASD) high-risk associated genes. Here, we report on uncharacterized functions of the chromatin remodelers Chd7 and Chd8 in OPCs. Their OPC-chromatin-binding profile combined with transcriptome and chromatin accessibility analyses of Chd7-deleted OPCs, demonstrates that Chd7 protects non-proliferative OPCs from apoptosis by chromatin-closing and transcriptional repression of p53.
Oligodendrocytes are joining astrocytes and microglia as members of a glial syndicate involved in the pathology of amyotrophic lateral sclerosis, according to a paper in the March 31 Nature Neuroscience online. Scientists from Johns Hopkins University in Baltimore, Maryland, report that a cycle of oligodendrocyte death and replacement precedes the onset of motor neuron death and symptoms in ALS model mice. In particular, they noted defects in these myelinating glia in the grey matter of the spinal cord and motor cortex of the mice, and also in people with ALS. The namesake white matter "lateral sclerosis" that results from the degeneration of motor neuron axons is well established, but the damage to myelin in grey matter seen here is a new concept, noted coauthor Jeffrey Rothstein. The work indicates that motor neurons depend on oligodendrocytes not just for insulation, but for their very survival.. "This is particularly exciting because it demonstrates a critical and completely unexpected role ...
Ectopic myelinating oligodendrocytes in the dorsal spinal cord as a consequence of altered semaphorin 6D signaling inhibit synapse formation.
Loss of oligodendrocytes in multiple sclerosis (MS) leads to demyelination and axonal dysfunction and transection. Myelin repair, or remyelination, not only restores proper axonal conduction, but also protects axons from degeneration. Oligodendrocytes are myelin-producing cells and are generated from oligodendrocyte progenitor cells (OPCs). Although spontaneous production of oligodendrocytes and consequent remyelination do occur in early phases of MS, the efficiency decreases over time as the disease progresses. Therapeutic interventions to stimulate oligodendrocyte production and remyelination efficiency are likely to reduce disease progression and neurological disability ...
This study identifies PTPα as an essential component of the OL differentiation program induced by the extrinsic ligand Lm2. This is in addition to the previously reported role of PTPα in promoting the intrinsic differentiation of OLs (Wang et al., 2009a), as confirmed in this study and discussed further below. Among numerous extracellular matrix proteins in the CNS, Lm2 has well-documented effects in promoting OPC differentiation, myelin membrane formation by OLs, and myelination (Buttery and ffrench-Constant, 1999; Chun et al., 2003; Colognato et al., 2004; Hu et al., 2009). Here, we show that OPCs devoid of PTPα survive comparably to WT OPCs but fail to differentiate in response to Lm2 as indicated by poor expression of the maturation markers MBP and CNP, unchanged expression of the progenitor marker PDGFRα and an inability to undergo the expansion in MBP-positive cell area that accompanies OL maturation. Thus, PTPα is required for Lm2-regulated gene expression and morphological changes ...
Cell migration plays an important role in the development of complex multicellular organisms. The molecular mechanisms that regulate this migration arc therefore of great interest. Unfortunately, however, analysis of cell migration in vertebrates is hampered by the inaccessability of the cells and the difficulty of manipulating their environment within the embryo. This review focusses on one particular migratory cell population, the oligodendrocyte p1ecursor cell or O-2A progenitor cell, that gives rise to the myelin-forming oligodendrocytes within the CNS. These cells mi grate extensively during normal development. They can be purified and grown in large numbers in cell culture, so allowing the use of reductionist approaches using cell and molecular biology techniques. Moreover, cultured cells will migrate within the CNS following transplantation. As a result, the migration of these cells in vivo can be analysed following manipulation in vitro. Taken together, we believe that the different ...
Oligodendrocyte precursors (OPCs) differentiate into oligodendrocytes that are the myelinating cells of the vertebrate CNS. Myelin sheaths wrap axons in the bra...
Mitochondria in oligodendrocyte progenitor cells (OPs) Dtake up and release cytosolic Ca2+ during agonist-evoked Ca2+ waves, but it is not clear whether or how they regulate Ca2+ signaling in OPs. We asked whether mitochondria. play an active role during agonist-evoked Ca2+ release from intracellular stores. Ca2+ puffs, wave initiation, and wave propagation were measured in fluo-4 loaded OP processes using linescan confocal microscopy. Mitochondrial depolarization, measured by tetramethyl rhodamine ethyl ester (TMRE) fluorescence, accompanied Ca2+ puffs and waves. in addition, waves initiated only where mitochondria were localized. To determine whether energized mitochondria were necessary for wave generation, we blocked mitochondrial function with the electron transport chain inhibitor antimycin A (AA) in combination with oligomycin. AA decreased wave speed and puff probability. These effects were not due to global changes in ATP. We found that AA increased cytosolic Ca2+ markedly reduced ...
Oligodendrocyte lineage transcription factor 2 (Olig2) is a basic helix-loop-helix transcription factor expressed in oligodendroglial tumors of the brain. It is also known as protein kinase C binding protein 2 (PRKCBP2), oligodendrocyte transcription factor 2, oligodendrocyte-specific bHLH transcription factor 2, BHLHB1, bHLHe19, OLIGO2, and RACK17. Olig2 protein plays an essential role in regulating the development of oligodendrocytes and motor neurons. Chromosomal translocations in the OLIG2 gene have been associated with T-cell acute lymphoblastic leukemia (T-ALL) and development of Down syndrome. Olig2 expression is useful in distinguishing diffuse gliomas from other types of brain tumors.. ...
Oligodendrocyte lineage transcription factor 2 (Olig2) is a basic helix-loop-helix transcription factor expressed in oligodendroglial tumors of the brain. It is also known as protein kinase C binding protein 2 (PRKCBP2), oligodendrocyte transcription factor 2, oligodendrocyte-specific bHLH transcription factor 2, BHLHB1, bHLHe19, OLIGO2, and RACK17. Olig2 protein plays an essential role in regulating the development of oligodendrocytes and motor neurons. Chromosomal translocations in the OLIG2 gene have been associated with T-cell acute lymphoblastic leukemia (T-ALL) and development of Down syndrome. Olig2 expression is useful in distinguishing diffuse gliomas from other types of brain tumors.. ...
Recent studies demonstrate that astroglial cells can be directly converted into functional neurons or oligodendrocytes. Here, we report that a single transcription factor Sox10 could reprogram astrocytes into oligodendrocyte-like cells, in vivo. For transdifferentiation, Sox10-GFP expressing viral particles were injected into cuprizone-induced demyelinated mice brains after which we assessed for the presence of specific oligodendrocyte lineage cell markers by immunohistofluorescence (IHF). As control, another group of demyelinated mice received GFP expressing viral particles. After 3 weeks, the majority of transduced (GFP+) cells in animals which received control vector were astrocytes, while in animals which received Sox10-GFP vector, the main population of GFP+ cells were positive for oligodendrocyte lineage markers. We also extracted primary astrocytes from mouse pups and purified them. Primary astrocytes were transduced in vitro and then transplanted into demyelinated brains for later fate ...
Our studies of oligodendrocyte development in the rodent optic nerve provide clues as to how cell numbers and the timing of differentiation may be controlled during mammalian development. Both cell number and the timing of differentiation depend on intracellular programs and extracellular signals, which together control cell survival and cell division. As the cells seem to compete for limiting amounts of both survival signals and mitogens, the levels of these extracellular signals must be tightly regulated, but it is not known how this is achieved. The timing of cell-cycle exit, and therefore the onset of differentiation, seems to depend in part on the progressive accumulation of the intracellular Cdk inhibitor p27/Kip1, but it is still unclear how the level of this protein is controlled over time in the dividing cells. The timing of cell-cycle exit is also regulated by thyroid hormone, which, along with other hormones, seems to coordinate the timing of development in various organs, much as the timing
Myelin is produced by cells called oligodendrocytes. Research shows that, in cases of chronic white matter injury, oligodendrocyte progenitor cells (OPCs) - the precursor cells of oligodendrocytes - accumulate in lesion areas but are unable to produce myelin. Scientists believe this is due to the presence of fragments from a very large molecule called hyaluronic acid (HA); these small fragments also accumulate at lesion sites.. Now, researchers studied how these HA fragments block myelin repair.. Results showed that one specific-size fragment of HA affected OPCs. Treating rat cells modeling white matter disease with this specific fragment initially activated myelin formation, then completely shut down.. Researchers noted that this is similar to the immune tolerance mechanism, which is used by the immune system to prevent severe tissue injury from an ongoing, damaging immune response.. "We showed that HA creates not just a roadblock to myelin repair after injury, it also shuts down all of the ...
The study, published online in the September 2011 edition of The Journal of Neuroscience, identified Sox17 as the gene that helps regulate the Wnt/beta-catenin signaling pathway during the transition of oligodendrocyte progenitor cells, or immature brain cells, to a more mature, differentiated state where they generate myelin.. "This is the first time the Sox17 gene has been identified as a regulator of the Wnt/beta-catenin pathway during myelination," said Li-Jin Chew, PhD, lead author of the study. "Our findings indicate that loss of Sox17 over-stimulates the Wnt/beta-catenin pathway and keeps oligodendrocyte progenitor cells from maturing and producing myelin, potentially causing developmental disabilities in developing babies and children.". Myelin is the protective material around the axons of neurons; in mass these types of ensheathed neurons are collectively called white matter. White matter serves as the primary messaging "network" that conducts signals rapidly between gray matter areas. ...
The advent of myelin was instrumental in advancing the nervous system during vertebrate evolution. With more rapid and efficient communication between neurons, faster and more complex computation could be performed in a given time and space. Our knowledge of how myelin-forming oligodendrocytes select and wrap axons has been limited by insufficient spatial and temporal resolution. By virtue of recent technological advances, significant progress has clarified longstanding controversies in the field. Here, we review insights into myelination, from target selection to axon wrapping and membrane compaction, and discuss how understanding these processes has unexpectedly opened new avenues of insight into myelination-centered mechanisms of neural plasticity.. Myelination occurs selectively around neuronal axons to increase the efficiency and velocity of action potentials. While oligodendrocytes are capable of myelinating permissive structures in the absence of molecular cues, structurally permissive ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Oligodendrocyte precursors (OPs) continue to proliferate and generate myelinating oligodendrocytes (OLs) well into adulthood. It is not known whether adult-born OLs ensheath previously unmyelinated axons or remodel existing myelin. We quantified OP division and OL production in different regions of …
... are known as the myelinating cells of the central nervous system responsible for producing myelin to insulate axons. Damage to myelin sheathe and oligodendrocytes is a key feature in multiple sclerosis. BioLegend develops and manufactures world-class, cutting-edge immunological reagents for biomedical research, offered at an outstanding value.
Rivera, Francisco J., Siebzehnrubl, Florian A., Kandasamy, Mahesh, Couillard-Despres, Sebastien, Caioni, Massimiliano, Poehler, Anne-Maria, Berninger, Benedikt, Sandner, Beatrice, Bogdahn, Ulrich, Goetz, Magdalena, Bluemcke, Ingmar, Weidner, Norbert und Aigner, Ludwig (2009) Mesenchymal stem cells promote oligodendroglial differentiation in hippocampal slice cultures. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 24 (3-4), S. 317-324 ...
Chemotherapy in cancer patients can be associated with serious short- and long-term adverse neurological effects, such as leukoencephalopathy and cognitive impairment, even when therapy is delivered systemically. The underlying cellular basis for these adverse effects is poorly understood. We found that three mainstream chemotherapeutic agents - carmustine (BCNU), cisplatin, and cytosine arabinoside (cytarabine), representing two DNA cross-linking agents and an antimetabolite, respectively - applied at clinically relevant exposure levels to cultured cells are more toxic for the progenitor cells of the CNS and for nondividing oligodendrocytes than they are for multiple cancer cell lines. Enhancement of cell death and suppression of cell division were seen in vitro and in vivo. When administered systemically in mice, these chemotherapeutic agents were associated with increased cell death and decreased cell division in the subventricular zone, in the dentate gyrus of the hippocampus and in the corpus
Background: IGF1R gene mutation usually cause IUGR. The children born with IUGR were prone to some kinds of brain function disorders.. Objective and hypotheses: The dysfunction of the brain was caused by the abnormal oligodendrocyte development.To establish lentivirus vector of IGF1R gene mutation (R709Q) and transfect oligodendrocyte precursors (Ge6). Observe the IRS/MAPK and PI3K/Akt/PKB signaling pathway and the change of proliferation, differentiation, and apoptosis of oligodendrocyte.. Method: Synthesise IGF1R (R709Q) gene in vitro and clone in lentivirus vector with resistance to puromycin (puro). R709Q gene was mediated by lentivirus and to transfect Ge6 cells. Target cells were selected by puro. The experimental group R709Q cells and the control group Ge6 cells were culture in vitro. IGF1 were used respectively. Immunofluorescent staining were applied to observe the positive rate of caspase-3 and O4; western blot were applied to observe the IRS/MAPK and PI3K/Akt/PKB signaling pathway, ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Jordan-Sciutto struck up a collaboration with Grinspan after hearing her describing her research on oligodendrocytes. Jordan-Sciutto had previously examined the effects of ART on neurons and astrocytes. Given the fact that people on ART had been found to have reduced white matter in their brains, it made sense to investigate how oligodendrocytes would be affected, since those cells produce the lipid-filled myelin that gives white matter its characteristic color.. Myelin production is concentrated in the first two years of life, and continues throughout childhood.. "Over the first two years of life you go from having hardly any control over your body to being able to control your limbs and walk," said Grinspan. "A lot of that is on account of myelination.". But even in adults, oligodendrocytes act to ensure myelin is properly maintained.. "If myelin is destroyed, nervous impulses will no longer travel smoothly along neurons and the now bare nerve process will also start to fall apart," Grinspan ...
Central nervous system function (CNS) requires precise communication between myriads of neurons and glia. A major challenge is to understand how these different cells organise and influence one another to generate and maintain a functional organ. We are interested in the communication between neurons and oligodendrocytes, a type of CNS glia. Oligodendrocytes ensheath (myelinate) axons by iteratively wrapping the axon. This cellular interaction is critical for proper nervous system function - it regulates transmission speed between nerve cells, learning and memory, and ensures long-term axonal health. Defective myelination impairs CNS function in multiple disorders ranging from diseases and pathologies of the developing and adult nervous system to neurodegenerative and psychiatric disorders. For example, degeneration of myelin is a major cause for sensory and motor dysfunction in diseases such as Multiple Sclerosis. ...
Axons of the central nervous system in adult mammals do not regenerate spontaneously after injury, partly because of the presence of oligodendrocytes that inhibit axonal growth. This is not the case in lower vertebrates (e.g., in fish), where regeneration of the optic nerve does occur spontaneously and has been correlated with the presence of factors cytotoxic to oligodendrocytes. The present study provides evidence that the substance originating from the fish optic nerves, which is cytotoxic to oligodendrocytes, is an interleukin 2-like substance.
Read about an MS study showing the protein EphrinB3 blocks remyelination by inhibiting oligodendrocyte formation, and suggesting it as a treatment target.