Hydrogen sulfide promotes proliferation and neuronal differentiation of neural stem cells and protects hypoxia-induced decrease in hippocampal neurogenesis

• Hydrogen sulfide promotes proliferation of neural stem cells.
• Hydrogen sulfide promotes neuronal differentiation of neural stem cells.
• Hydrogen sulfide protects hypoxia-induced decrease in hippocampal neurogenesis.

Accumulating evidence has suggested that hydrogen sulfide (H2S) acts as a novel neuro-modulator and neuroprotective agent; however, it remains to be investigated whether H2S has a direct effect on neural stem cells (NSCs). In the present study, we examined the effects of H2S donor, sodium hydrosulfide (NaHS) on mouse NSCs and hippocampal neurogenesis. We report here that NaHS promoted proliferation and neuronal differentiation of NSCs. Further analysis revealed that NaHS-induced proliferation was associated with phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and neuronal differentiation was linked to altered expression of differentiation-related genes. In addition, C57BL/6 mice (1 day old) subjected to hypoxia were treated with NaHS to explore whether H2S would influence the neurogenesis of hippocampus. BrdU incorporation assay results showed that administration of NaHS could increase the number of proliferating cells in the dentate gyrus of hippocampus in the mice after hypoxia. Moreover, Morris water maze test showed that treatment with NaHS improved cognitive impairment after hypoxia in mice. These findings suggest that H2S may afford a novel therapeutic strategy to intervene in the progression of brain diseases.