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Introduction Oligodendrocytes are the cells in the CNS that produce myelin, a multilamellar lipid structure that wraps around axons and ensures proper conduction of action potentials. Oligodendrocytes are derived from [...], Oligodendrocytes are glial cells that populate the entire CNS after they have differentiated from oligodendrocyte progenitor cells. From birth onward, oligodendrocytes initiate wrapping of neuronal axons with a multilamellar lipid structure called myelin. Apart from their well-established function in action potential propagation, more recent data indicate that oligodendrocytes are essential for providing metabolic support to neurons. Oligodendrocytes transfer energy metabolites to neurons through cytoplasmic "myelinic" channels and monocarboxylate transporters, which allow for the fast delivery of short-carbon-chain energy metabolites like pyruvate and lactate to neurons. These substrates are metabolized and contribute to ATP synthesis in neurons. This Review will discuss our current understanding of this metabolic supportive function of oligodendrocytes and its potential impact in human neurodegenerative disease and related animal models.

Introduction Despite long-held dogma on the impossibility of changing the identity of differentiated cells, the expression of specific transcription factors, cell-cell fusion, and nuclear transfer experiments has shown the feasibility [...], Vision impairments and blindness caused by retinitis pigmentosa result from severe neurodegeneration that leads to a loss of photoreceptors, the specialized light-sensitive neurons that enable vision. Although the mammalian nervous system is unable to replace neurons lost due to degeneration, therapeutic approaches to reprogram resident glial cells to replace retinal neurons have been proposed. Here, we demonstrate that retinal Muller glia can be reprogrammed in vivo into retinal precursors that then differentiate into photoreceptors. We transplanted hematopoietic stem and progenitor cells (HSPCs) into retinas affected by photoreceptor degeneration and observed spontaneous cell fusion events between Muller glia and the transplanted cells. Activation of Wnt signaling in the transplanted HSPCs enhanced survival and proliferation of MullerHSPC hybrids as well as their reprogramming into intermediate photoreceptor precursors. This suggests that Wnt signaling drives the reprogrammed cells toward a photoreceptor progenitor fate. Finally, Muller-HSPC hybrids differentiated into photoreceptors. Transplantation of HSPCs with activated Wnt functionally rescued the retinal degeneration phenotype in rd10 mice, a model for inherited retinitis pigmentosa. Together, these results suggest that photoreceptors can be generated by reprogramming Muller glia and that this approach may have potential as a strategy for reversing retinal degeneration.

Introduction Huntington's disease (HD) is a progressive neurodegenerative disease manifested by highly selective degeneration of the striatal neurons. HD is characterized as movement disorder in the form of involuntary, rapid, [...], : Naringin (4',5,7-trihydroxy-flavonone-7-rhamnoglucoside), a flavonone present in grapefruit, has recently been reported to protect against neurodegeration, induced with 3-nitropropionic acid (3-NP), through its antioxidant, anti-inflammatory, and antiapoptotic properties. This study used a rat model of 3-NP-induced neurodegeneration to investigate the neuroprotective effects of naringin exerted by modulating the expression of matrix metalloproteinases and glial fibrillary acidic protein. Neurodegeneration was induced with 3-NP (10 mg/kg body mass, by intraperitoneal injection) once a day for 2 weeks, and induced rats were treated with naringin (80 mg/kg body mass, by oral gavage, once a day for 2 weeks). Naringin ameliorated the motor abnormalities caused by 3-NP, and reduced blood-brain barrier dysfunction by decreasing the expression of matrix metalloproteinases 2 and 9, along with increasing the expression of the tissue inhibitors of metalloproteinases 1 and 2 in 3-NP-induced rats. Further, naringin reduced 3-NP-induced neuroinflammation by decreasing the expression of nuclear factor-kappa B and glial fibrillary acidic protein. Thus, naringin exerts protective effects against 3-NP-induced neurodegeneration by ameliorating the expressions of matrix metalloproteinases and glial fibrillary acidic protein. Key words: naringin, 3-nitropropionic acid, MMP, TIMP, GFAP. On a recemment rapporte que la naringine (4',5,7-trihydroxy-flavonone-7-rhamnoglucoside), une flavanone que l'on trouve dans le pamplemousse, permet de proteger de la neurodegenerescence induite par les proprietes antioxydantes, antiinflammatoires et antiapoptotiques de l'acide 3-nitropropionique (3-NP). Nous avons concu la presente etude en vue d'etudier les effets neuroprotecteurs de la naringine sur la neurodegenerescence induite par le 3-NP en modulant l'expression des metalloproteinases matricielles et de la proteine acide fibrillaire gliale. La neurodegenerescence a ete induite par l'administration de 3-NP (10 mg/kg de poids corporel, par voie intraperitoneale, une fois par jour, pendant 2 semaines). Les rats soumis aux effets du 3-NP etaient traites par la naringine (80 mg/kg de poids corporel par gavage, une fois par jour, pendant 2 semaines). L'administration de naringine a permis d'attenuer les anomalies motrices causees par le 3-NP. Par ailleurs, la naringine a permis d'attenuer le dysfonctionnement de la barriere hemo-encephalique en diminuant l'expression des metalloproteinases matricielles 2/9 et en augmentant l'expression des inhibiteurs tissulaires des metalloproteinases 1/2 chez les rats soumis aux effets du 3-NP. De plus, la naringine a permis de reduire la neuro-inflammation induite par le 3-NP en diminuant l'expression des facteurs nucleiques kappa B et de la proteine acide fibrillaire gliale. En somme, nous avons montre que la naringine possede des effets protecteurs contre la neurodegenerescence induite par le 3-NP qui consistent a ameliorer l'expression des metalloproteinases matricielles et de la proteine acide fibrillaire gliale. [Traduit par la Redaction] Mots-cles: naringine, acide 3-nitropropionique, MMP, TIMP, GFAP.

Introduction Schizophrenia and bipolar disorder (BD) are 2 disabling mental illnesses, each with a prevalence of approximately 25-30 million people worldwide. (1) While the causes are unknown, brain imaging studies [...], Background: Brain imaging studies suggest that volume reductions and compromised white matter integrity occur in schizophrenia and bipolar disorder (BD). However, the cellular correlates have not yet been identified. To address this issue we assessed oligodendrocyte, astrocyte and microglial populations in postmortem white matter from schizophrenia, BD and nonpsychiatric control samples. Methods: The density, areal fraction and spatial distribution of glial fibrillary acidic protein (GFAP)-expressing astrocytes and ionized calciumbinding adaptor molecule-1 (IBA-1)-expressing microglia as well as the density, nuclear size and spatial distribution of Nissl- stained oligodendrocytes were quantified in postmortem white matter adjacent to the dorsolateral prefrontal cortex (Brodmann area 9) in schizophrenia, BD and control samples (n = 20). In addition, the oligodendrocyte-associated proteins myelin basic protein and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) were quantified in the same samples by enzyme-linked immunosorbent assay and immunoblotting. Results: Oligodendrocyte density (p = 0.012) and CNPase protein levels (p = 0.038) differed between groups, being increased in BD compared with control samples. The GFAP area fraction (p = 0.05) and astrocyte spatial distribution (p = 0.040) also differed between groups, reflecting decreased area fraction and increased cell clustering in both schizophrenia and BD samples. Limitations: Oligodendrocytes were identified using morphological criteria. Conclusion: This study provides evidence for glial pathology in prefrontal white matter in schizophrenia and BD. Changes in oligodendrocyte and astrocyte populations in white matter in the major psychiatric disorders may reflect disruptions in structural or metabolic support of axons.