Abstract
The molecular mediators underlying the effects of inflammation on neural stem cells (NSCs) are not fully characterized. In this study, we identified Ascl2 as a downstream basic helix-loop-helix (bHLH) transcription factor in NSCs following exposure to TNFα. Under normal conditions, Ascl2 expression is inhibited at post-transcriptional levels by miR-26a, which targets the 3' untranslated region (UTR) of Ascl2. Upon exposure to TNFα, miR-26a expression is reduced, which leads to up-regulation of Ascl2. Overexpression of Ascl2 promotes neuronal differentiation, reduces proliferation, and increases the level of cleaved CASPASE 3 in NSCs, as observed in the in vitro and in ovo experiments. Ascl2 may serve in NSCs as a standby factor that readily responds to TNFα, which is often induced in inflammatory situations. In a chronic inflammatory condition with consistent up-regulation of TNFα, overexpression of Ascl2 may inhibit neurogenesis as a net result.