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Oligodendrocyte Precursor Cells (oligodendrocyte + precursor_cell)
Selected AbstractspH is an intracellular effector controlling differentiation of oligodendrocyte precursors in culture via activation of the ERK1/2 pathwayJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2006Frédéric Bernard Abstract We reported previously that onset of oligodendrocyte precursor cell (OPC) differentiation is accompanied by an increase in intracellular pH (pHi). We show that OPC differentiation is dependent primarily on a permissive pHi value. The highest differentiation levels were observed for pHi values around 7.15 and inhibition of differentiation was observed at slightly more acidic or alkaline values. Clamping the pHi of OPCs at 7.15 caused a transient activation of ERK1/2 that was not observed at more acidic or alkaline values. Furthermore, inhibition of ERK activation with the UO126 compound totally prevented OPC differentiation in response to pHi shift. These results indicate that pHi, acting through the ERK1/2 pathway, is a key determinant for oligodendrocyte differentiation. We also show that this pHi pathway is involved in the process of retinoic acid-induced OPC differentiation. © 2006 Wiley-Liss, Inc. [source] Astrocytes promote neurogenesis from oligodendrocyte precursor cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006P. M. Gaughwin Abstract The oligodendrocyte precursor cell (OPC) has until recently been regarded as a lineage-restricted precursor cell. Considerable interest has been generated by reports suggesting that OPCs may possess a wider differentiation potential than previously assumed and thus be considered a multipotential stem cell. This study examined the neuronal differentiation potential of rat, postnatal cortical OPCs in response to extracellular cues in vitro and in vivo. OPCs did not exhibit intrinsic neuronal potential and were restricted to oligodendrocyte lineage potential following treatment with the neural precursor mitogen fibroblast growth factor 2. In contrast, a postnatal hippocampal astrocyte-derived signal(s) is sufficient to induce functional neuronal differentiation of cortical OPCs in vitro in population and single cell studies. Co-treatment with Noggin, a bone morphogenetic protein antagonist, did not attenuate neuronal differentiation. Following transplantation to the adult rat hippocampus, cortical OPCs expressed doublecortin, a neuroblast-associated marker. The present findings show that hippocampal, astrocyte-derived signals can induce the neuronal differentiation of OPCs through a Noggin-independent mechanism. [source] Delay of myelin formation in arylsulphatase A-deficient miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2005Afshin Yaghootfam Abstract Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulphatase A (ASA). This leads to the accumulation of the sphingolipid 3-O-sulphogalactosylceramide (sulphatide) and progressive demyelination in the nervous system of MLD patients. The mechanisms and development of pathology in the disease are still largely unknown. In this study we investigate how the inability to degrade sulphatide affects the formation of myelin in ASA-deficient (ASA,/,) mice. In mice at 2 weeks of age there was a substantial reduction in myelin basic protein (MBP) mRNA and protein. This was confirmed by an immunohistochemical analysis. MBP mRNA and protein, however, reach normal levels at 3 weeks of age. Proteolipid protein (PLP) and MAL mRNA were also reduced in ASA,/, mice at 2 weeks of age; whereas the level of PLP mRNA was normal at 26 weeks of age, MAL mRNA expression remained reduced up to this age. In situ hybridization revealed no significant changes in the number of myelinating oligodendrocytes or oligodendrocyte precursor cells in ASA,/, mice. These results suggest that oligodendrocyte differentiation was normal in ASA,/, mice. No differences were found in the expression of the sulphatide synthesizing enzymes cerebroside sulphotransferase and UDP-galactose : ceramide galactosyltransferase. Our data demonstrate a delay in myelin formation in ASA,/, mice. This raises the possibility that similar alterations in MLD patients may contribute to the pathology of the disease. [source] Regulation of L-type Ca++ currents and process morphology in white matter oligodendrocyte precursor cells by golli-myelin proteinsGLIA, Issue 11 2010Daniel Fulton Abstract The golli myelin basic proteins are expressed in oligodendroglial precursor cells (OPCs) where they play a role in regulating Ca2+ homeostasis. During depolarization, they influence process outgrowth and migration through their action on voltage-operated Ca2+ channels (VOCCs). To identify ion channels that are modulated by golli, we examined the electrophysiological properties of VOCCs in OPCs in the white matter of golli knock-out and control mice. OPCs exhibited two distinct Ca2+ channels, which were distinguished by their voltage dependence and pharmacological profiles and which exhibited many of the hallmarks of LVA/T-type and HVA/L-type Ca2+ channels. The density of high-voltage-activated (HVA) currents was reduced in OPCs recorded in golli-KO tissue, while low-voltage-activated (LVA) currents remained unaltered in these cells. These data indicate that golli exerts an exclusive influence on L-type Ca2+ channels in OPCs. Oligodendrocytes (OLs) also displayed LVA and HVA currents, although the density of these currents was much reduced at this developmental stage. These currents were not altered in golli-KO OLs showing the influence of golli on L-type Ca2+ channels is restricted to a specific time-window during the course of oligodendroglial development. The actions of golli on OPC L-type Ca2+ channels were accompanied by changes in process morphology, including a reduction in process complexity and the appearance of enlarged varicosities that decorated these cellular processes. These data on L-type Ca2+ channels and process development provide in situ evidence for the influence of golli on VOCCs, and offer an explanation for the hypomyelination observed in the brains of golli-KO mice. © 2010 Wiley-Liss, Inc. [source] Glaucomatous optic nerve injury involves early astrocyte reactivity and late oligodendrocyte lossGLIA, Issue 7 2010Janice L. Son Abstract Glaucoma, a neurodegenerative disease affecting retinal ganglion cells (RGC), is a leading cause of blindness. Since gliosis is common in neurodegenerative disorders, it is important to describe the changes occurring in various glial populations in glaucoma animal models in relation to axon loss, as only changes that occur early are likely to be useful therapeutic targets. Here, we describe changes occurring in glia within the myelinated portion of the optic nerve (ON) in both DBA/2J mice and in a rat ocular hypertension model. In both glaucoma animal models, we found only a modest loss of oligodendrocytes that occurred after axons had already degenerated. In DBA/2J mice there was proliferation of oligodendrocyte precursor cells (OPCs) and new oligodendrocyte generation. Activation of microglia was detected only in highly degenerated DBA/2J ONs. In contrast, a large increase in astrocyte reactivity occurred early in both animal models. These results are consistent with astrocytes playing a prominent role in regulating axon loss in glaucoma. © 2010 Wiley-Liss, Inc. [source] Attenuation of proliferation in oligodendrocyte precursor cells by activated microgliaJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2010Deanna L. Taylor Abstract Activated microglia can influence the survival of neural cells through the release of cytotoxic factors. Here, we investigated the interaction between Toll-like receptor 4 (TLR4)-activated microglia and oligodendrocytes or their precursor cells (OPC). Primary rat or N9 microglial cells were activated by exposure to TLR4-specifc lipopolysaccharide (LPS), resulting in mitogen-activated protein kinase activation, increased CD68 and inducible nitric oxide synthase expression, and release of the proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6). Microglial conditioned medium (MGCM) from LPS-activated microglia attenuated primary OPC proliferation without inducing cell death. The microglial-induced inhibition of OPC proliferation was reversed by stimulating group III metabotropic glutamate receptors in microglia with the agonist L-AP4. In contrast to OPC, LPS-activated MGCM enhanced the survival of mature oligodendrocytes. Further investigation suggested that TNF and IL-6 released from TLR4-activated microglia might contribute to the effect of MGCM on OPC proliferation, insofar as TNF depletion of LPS-activated MGCM reduced the inhibition of OPC proliferation, and direct addition of TNF or IL-6 attenuated or increased proliferation, respectively. OPC themselves were also found to express proteins involved in TLR4 signalling, including TLR4, MyD88, and MAL. Although LPS stimulation of OPC did not induce proinflammatory cytokine release or affect their survival, it did trigger JNK phosphorylation, suggesting that TLR4 signalling in these cells is active. These findings suggest that OPC survival may be influenced not only by factors released from endotoxin-activated microglia but also through a direct response to endotoxins. This may have consequences for myelination under conditions in which microglial activation and cerebral infection are both implicated. © 2010 Wiley-Liss, Inc. [source] Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells,ANNALS OF NEUROLOGY, Issue 3 2009Sha Mi PhD Objective Repair of demyelinated axons in diseases such as multiple sclerosis requires activation of the myelination program in existing or newly recruited oligodendrocyte precursor cells (OPCs). The control of OPC differentiation and initiation of myelination during repair is poorly understood. In this study, we test the ability of anti,LINGO-1 reagents to promote myelination in vitro and remyelination in the rodent adult central nervous system in vivo. Methods The effects of LINGO-1 antagonists on the differentiation of OPCs and the promotion of myelination has been assayed using a combination of coculture and slice culture preparations. Using three different animal models of demyelination and remyelination, we morphologically and functionally assessed the effects of LINGO-1 antagonists on OPC differentiation and myelin repair. Results The data indicate that in vitro treatment with antagonists of LINGO-1 promote OPC differentiation and myelination, whereas in vivo remyelination is accelerated in lysophosphatidylcholine- or cuprizone-induced demyelination. This remyelination is associated with enhanced OPC differentiation and functional recovery of conduction velocities in demyelinated axons. Interpretation Our studies demonstrate that LINGO-1 antagonism promotes OPC differentiation and remyelination, and suggest LINGO-1 functions as an inhibitor of OPC differentiation to retard central nervous system remyelination. Ann Neurol 2009;65:304,315 [source] | ||||||||||