Dexamethasone blocks astroglial differentiation from neural precursor cells


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Abstract

In previous studies, we demonstrated functional neuronal and dopaminergic differentiation of fetal mesencephalic neural precursor cells. The major factors for orienting their progeny towards a dopaminergic phenotype are forskolin and interleukin-1β. Here, we investigated the effects of dexamethasone (10 μM) on neuronal and glial differentiation. Exposure of mesencephalic neural precursor cells to dexamethasone significantly reduces the amount of glial fibrillary acidic protein+ astroglia, but not of galactocerebrosidase C+ oligodendroglia, MAP2ab+ neurons and tyrosine hydroxylase+ dopaminergic cells. Presuming a possible involvement of the nuclear factor-κB pathway, we examined the effects of wortmannin (phosphatidylinositol 3′-kinase inhibitor) and SN50 (nuclear factor-κB inhibitor) on gliogenesis. Both wortmannin and SN50 mimicked the effects of dexamethasone suggesting that dexamethasone specifically blocks astroglial differentiation from mesencephalic neural precursor cells most likely via inhibition of the nuclear factor-κB pathway.

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