Home About us Contact
|
Home About us Contact | ||
|
|
||
Human Oligodendrocytes (human + oligodendrocyte)
Selected AbstractsRole for CXCR2 and CXCL1 on glia in multiple sclerosisGLIA, Issue 1 2006Kakuri M. Omari Abstract As part of a need to understand myelin repair mechanisms, molecular pathways underlying oligodendrocyte behavior and central nervous system (CNS) remyelination are currently key topics in multiple sclerosis (MS). In the present study, we report expression of a chemoattractant receptor of the immune system, the chemokine receptor, CXCR2, on normal and proliferating oligodendrocytes in active MS lesions. Proliferating oligodendrocytes were occasionally associated with reactive astrocytes positive for CXCL1 (GRO-,), the ligand for CXCR2. CXCL1 expression was not seen on astrocytes in control and normal CNS tissue, while CXCR2 expression was constitutive on oligodendrocytes. At the functional level, following stimulation with the proinflammatory cytokine, interleukin-1, (IL-1,), we found high-level synthesis of CXCL1 by human fetal astrocytes in vitro. In contrast, human oligodendrocytes in culture expressed the receptor, CXCR2, constitutively. We propose that the concurrence of CXCR2 on oligodendrocytes and induced CXCL1 on hypertrophic astrocytes in MS provides a novel mechanism for recruitment of oligodendrocytes to areas of damage, an essential prerequisite for lesion repair in this devastating human condition. © 2005 Wiley-Liss, Inc. [source] Differential generation of oligodendrocytes from human and rodent embryonic spinal cord neural precursorsGLIA, Issue 4 2004Siddharthan Chandran Abstract Human neural precursors are considered to have widespread therapeutic possibilities on account of their ability to provide large numbers of cells whilst retaining multipotentiality. Application to human demyelinating diseases requires improved understanding of the signalling requirements underlying the generation of human oligodendrocytes from immature cell populations. In this study, we compare and contrast the capacity of neural precursors derived from the developing human and rodent spinal cord to generate oligodendrocytes. We show that the developing human spinal cord (6,12 weeks of gestation) displays a comparable ventrodorsal gradient of oligodendrocyte differentiation potential to the embryonic rodent spinal cord. In contrast, fibroblast growth factor 2 (FGF-2) expanded human neural precursors derived from both isolated ventral or dorsal cultures show a reduced capacity to generate oligodendrocytes, whereas comparable rodent cultures demonstrate a marked increase in oligodendrocyte formation following FGF-2 treatment. In addition, we provide evidence that candidate growth factors suggested from rodent studies, including FGF-2 and platelet-derived growth factor (PDGF) do not stimulate proliferation of human oligodendrocyte lineage cells. Finally, we show that the in vivo environment of the acutely demyelinating adult rat spinal cord is insufficient to stimulate the differentiation of immature human spinal cord cells to oligodendrocytes. These results provide further evidence for inter-species difference in the capacity of neural precursors to generate oligodendrocytes. © 2004 Wiley-Liss, Inc. [source] Alternative isoforms of myelin/oligodendrocyte glycoprotein with variable cytoplasmic domains are expressed in human brainJOURNAL OF NEUROCHEMISTRY, Issue 2 2007Chantal Allamargot Abstract The human myelin/oligodendrocyte glycoprotein (MOG) gene is encoded by 10 exons that exhibit a complex pattern of alternative splicing. This report demonstrates that several MOG-specific alternative splice variants are indeed expressed in human oligodendrocytes (OLs) and myelin during perinatal development and are retained through adulthood. While all forms possess the common extracellular Ig-like domain, these alternative MOG structures differ significantly in their respective cytoplasmic domains. Peptide-specific antibodies were generated to facilitate detection of these different MOG moieties. The fidelity of these antibodies is shown using N20 OLs expressing individual MOG variants. These antibodies also only co-localize with another well-characterized marker of OLs and myelin , PLP/DM20 proteins. Among the human tissue samples tested, very limited expression occurred by 36 weeks gestation for 2,3 MOG variants, and the remaining MOG isoforms were not evident until shortly after birth. This study represents the first evidence of alternative translation products from the MOG gene. To date, it is believed that alternative splicing of MOG is limited to primates. Recent completion of various genome projects has revealed that alternative splicing is much more prevalent than originally estimated, and species-specific alternative splicing is now being shown to be highly relevant to expanding proteomic diversity. [source] Oligodendrocyte injury in multiple sclerosis: a role for p53JOURNAL OF NEUROCHEMISTRY, Issue 3 2003Karolina Wosik Abstract Multiple sclerosis (MS) is a neurological disorder characterized by myelin destruction and a variable degree of oligodendrocyte death. We have previously shown that overexpression of the transcription factor p53 can induce oligodendrocyte apoptosis. We investigated the mechanism of p53-induced apoptosis using primary cultures of central nervous system-derived adult human oligodendrocytes. Adenovirus-mediated p53 overexpression resulted in up-regulation of the death receptors Fas, DR4 and DR5 with subsequent caspase-mediated apoptosis of the oligodendrocytes. The oligodendrocytes were protected from p53-induced cell death by blocking signaling through Fas and/or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors. Although lower levels of p53 did not induce apoptosis, the increase in death receptor expression was sufficient to render the oligodendrocytes susceptible to apoptosis in the presence of exogenous Fas ligand and TRAIL. These ligands are present in the inflammatory milieu of active MS lesions. In situ analysis of active MS lesions revealed increased p53 expression in oligodendrocytes in lesions that featured oligodendrocyte apoptosis and cell loss. Our data provide evidence for a novel role for p53 in the pathogenesis of MS. [source] | ||||||||||