Regulation of SVZ‐derived gliogenesis by inflammatory‐demyelination

Identifying a source of cells with the capacity to generate oligodendrocytes in the adult CNS would help the development of strategies to promote myelin repair. During development of the neonate rodent forebrain, most oligodendrocytes derive from the subventricular zone (SVZ), a germinative area which also contributes to the genesis of astrocytes and neurons. While the SVZ persists in the adult brain, its size is largely reduced and its contribution to cell genesis is essentially restricted to the renewal of the granular and periglomerular neurons of the olfactory bulb. Lesion derived signals can have a profound impact on the behavior of the SVZ cells. While cortical trauma triggers their mobilization and differentiation in astrocytes in the lesioned cortex (Holmin et al. 1997), focaly-induced demyelination promotes their migration in the demyelinated white matter and differentiation in astrocytes and oligodendrocytes (Nait-Oumesmar et al. 1999). Using EAE, we will show that multifocal demyelination (i) promotes the proliferation of the SVZ precursors (ii) enhances their migration towards the olfactory bulb and triggers their mobilization to multiple sites of the diseased white matter, and (iii) induces their differentiation in neurons, astrocytes and oligodendrocytes in the olfactory bulb, and in oligodendrocytes and astrocytes in the demyelinated white matter. SVZ precursors could thus be a source of oligodendrocytes and contribute with oligodendrocyte progenitors to the replacement of lost oligodendrocytes in demyelinating diseases of the adult CNS.