The role of SVZ-derived neural precursors in demyelinating diseases: From animal models to multiple sclerosis

Nait‐Oumesmar, Brahim; Picard-Riéra, Nathalie; Kerninon, Christophe; Evercooren, A. Baron‐Van

doi:10.1016/j.jns.2007.09.032

Cited by 110 publications

(103 citation statements)

References 39 publications

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“…Though at much higher levels, our observation corroborates recent finding in multiple sclerosis in which a twoto threefold increase in cell density and proliferation of early glial progenitors was seen in the subventricular region of patients (Nait-Oumesmar et al, 2007) as well as in rodent models (Nait-Oumesmar et al, 2008). Interestingly, an earlier brain tissue histology report of a 4-year-old CD patient described an increased density of OLs (Mirimanoff, 1976), and yet another report described loss of OLs (Adachi et al, 1966).…”

Section: Discussionsupporting

confidence: 91%

Lack of aspartoacylase activity disrupts survival and differentiation of neural progenitors and oligodendrocytes in a mouse model of Canavan disease

Kumar

Biancotti

Matalon

et al. 2009

J of Neuroscience Research

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Loss of the oligodendrocyte (OL)-specific enzyme aspartoacylase (ASPA) from gene mutation results in the sponginess and loss of white matter (WM) in Canavan disease (CD). This study addresses the fate of OLs during the pathophysiology of CD in an adult ASPA knockout (KO) mouse strain. Massive arrays of neural stem/progenitor cells, immunopositive for PSA-NCAM, nestin, vimentin, and NG2, were observed within the severely affected spongy WM of the KO mouse brain. In these mice, G1-->S cell cycle progression was confirmed by an increase in cdk2-kinase activity, a reduction in mitotic inhibitors p21(Cip1) and p27(Kip1), and an increase in bromodeoxyuridine (BrdU) incorporation. Highly acetylated nuclear histones H2B and H3 were detected in adult KO mouse WM, suggesting the existence of noncompact chromatin as seen during early development. Costaining for BrdU- or Ki67-positive cells with markers for neural progenitors confirmed a continuous generation of OL lineage cells in KO WM. We observed a severe reduction in 21.5- and 18.5-kDa myelin basic protein and PLP/DM20 proteolipid proteins combined with a decrease in myelinated fibers and a perinuclear retention of myelin protein staining, indicating impairment in protein trafficking. Death of OLs, neurons, and astrocytes was identified in every region of the KO brain. Immature OLs constituted the largest population of dying cells, particularly in WM. We also report an early expression of full-length ASPA mRNA in normal mouse brain at embryonic day 12.5, when OL progenitors first appear during development. These findings support involvement of ASPA in CNS development and function.

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Section: Discussionsupporting

confidence: 91%

Lack of aspartoacylase activity disrupts survival and differentiation of neural progenitors and oligodendrocytes in a mouse model of Canavan disease

Kumar

Biancotti

Matalon

et al. 2009

J of Neuroscience Research

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“…Such activation has been found in the SVZ of the lateral ventricle (Calza et al, 1998;Picard-Riera et al, 2002;Pluchino et al, 2008), the dentate gyrus (Aharoni et al, 2005), as well as the spinal cord of EAE animals (Danilov et al, 1999). In MS patients, aberrant neurogenesis has been found in SVZ (Nait-Oumesmar et al, 2008) and subcortical white matter structures (Chang et al, 2008).…”

Section: Discussionmentioning

confidence: 97%

Modulation of adult hippocampal neurogenesis during myelin‐directed autoimmune neuroinflammation

Huehnchen

Prozorovski

Klaißle

et al. 2010

Glia

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In chronic autoimmune diseases of the central nervous system (CNS) such as multiple sclerosis (MS) clinical signs of cognitive dysfunction have been associated with structural changes in the hippocampus. Moreover, experimental studies indicate that inflammatory responses within the CNS modulate the homeostasis of newborn cells in the adult dentate gyrus (DG). However, it remained open whether such changes happen regardless of the primary immunological target or whether a CNS antigen-directed T lymphocyte-mediated autoimmune response may exert a specific impact. We therefore induced experimental autoimmune encephalomyelitis (EAE), a common model of MS serving as a paradigm for a CNS-specific immune response, by immunizing C57BL/6 mice with encephalitogenic myelin oligodendrocyte glycoprotein (MOG) p35-55. In EAE animals, we found enhanced de novo generation and survival of doublecortin (DCX)-positive immature neurons when compared with controls immunized with CNS-irrelevant antigen (ovalbumine). However, despite activation of neurogenesis, we observed a reduced capacity of these cells to generate mature neurons. Moreover, the high number of newly born cells retained the expression of the glial marker GFAP. These effects were associated with downregulation of pro-neurogenic factors Neurogenin1 and Neurogenin2 and dysregulation of Notch, β-catenin, Sonic Hedgehog (Shh) signaling as suggested by altered gene expression of effector molecules. Thus, a CNS antigen-specific immune response leads to an aberrant differentiation of neural precursors associated with dysbalance of signaling pathways relevant for adult hippocampal neurogenesis. These results may further extend our understanding of disturbed regeneration in the course of chronic inflammatory CNS diseases such as MS.

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“…It is shown that these cells are able to be activated in response to a demyelinating insult and participated in adults CNS remyelination (Franklin et al 1997). Subventricular zone of lateral ventricles is the main pool of stem cells in the brain (Galli et al 2003), which is reported that are able to answer to the demyelinating insults in corpus callosum by proliferation, mobilization to the site of injury, and differentiation into the myelinating cells (Gensert and Goldman 1997;Nait-Oumesmar et al 2008). The stem cells are also present in hippocampus (Nakafuku et al 2002;Becq et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Vitamins E and D3 Attenuate Demyelination and Potentiate Remyelination Processes of Hippocampal Formation of Rats Following Local Injection of Ethidium Bromide

et al. 2009

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Cognitive deficits have been observed in patients with multiple sclerosis (MS) due to hippocampal insults. Antioxidant vitamins D and E are suggested for patients suffering from neurodegenerative diseases like MS, while their mechanisms of action are not well understood. Here, we have tried to study the effects of these vitamins on demyelination, cell death, and remyelination of rat hippocampus following local ethidium bromide (EB) injection. Animals received 100 mg/kg vitamin E or 5 microg/kg of vitamin D3 for 2, 7, or 28 days. The extent of demyelination, myelin staining intensity, and expression of myelin basic protein and caspase-3 were investigated using histological and immunoblotting verification. Administration of EB alone caused demyelination, cell death, and afterward an endogenous repair. Vitamins E and D3 reduced the EB-induced damage and increased the endogenous remyelination of hippocampus. Although the anti-apoptotic effect of these vitamins and protection against demyelination were predictable based on their antioxidant effect, our results indicated the positive effect of vitamins E and D3 on process of remyelination by endogenous progenitor cells and supported their possible therapeutic effects in the context of demyelinating diseases like MS.

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The role of SVZ-derived neural precursors in demyelinating diseases: From animal models to multiple sclerosis

Cited by 110 publications

References 39 publications

Lack of aspartoacylase activity disrupts survival and differentiation of neural progenitors and oligodendrocytes in a mouse model of Canavan disease

Lack of aspartoacylase activity disrupts survival and differentiation of neural progenitors and oligodendrocytes in a mouse model of Canavan disease

Modulation of adult hippocampal neurogenesis during myelin‐directed autoimmune neuroinflammation

Vitamins E and D3 Attenuate Demyelination and Potentiate Remyelination Processes of Hippocampal Formation of Rats Following Local Injection of Ethidium Bromide

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