Nogo receptor blockade enhances subventricular zone’s stem cells proliferation and differentiation in demyelination context

Introduction: Nogo-A and Nogo receptor (NgR) are expressed in the subventricular zone (SVZ) stem cells. NgR plays critical inhibitory roles in axonal regeneration and remyelination. However, the role of NgR in SVZ niche behaviors in demyelination context is still uncertain. Here we investigated the effects of NgR inhibition on SVZ niche reaction in a local model of demyelination in adult mouse optic chiasm. Methods: Demyelination was induced in adult mouse optic chiasm by microinjection of lysolecithin. We injected siRNAs against NgR intracerebroventricularly via a permanent cannula over 14 days to knockdown NgR. To trace SVZ stem cells and assess the effect of NgR inhibition on their reaction, BrdU was injected to the animals prior to the demyelination induction. Immunohistochemistry and histological analysis was carried out 3, 7 and 14 days post demyelination lesion. Results: NgR inhibition significantly increased the numbers of proliferating cells in SVZ in response to demeylination. The number of BrdU+/Olig2+progenitor cells in the neurogenic zone of the lateral ventricles was enhanced when NgR was blocked. These progenitor cells (Olig2+, GFAP+ or PSA-NCAM) were mobilized away from this SVZ as a function of time. Inhibition of NgR significantly reduced demyelination extension in optic chiasm. Conclusion: Our findings reveal that inhibition of NgR potentiates adult SVZ progenitor cells proliferation and differentiation in demyelination condition and facilitates remyelination in the optic chiasm. Therefore, inhibition of NgR function could have therapeutic potential for demyelinating disease like multiple sclerosis.