Hydrogen sulfide enhances adult neurogenesis in a mouse model of Parkinson's disease.

Abstract

Hydrogen sulfide (H2S) is regarded to be a protectant against diseases of the central nervous system and cardiovascular system. However, the mechanism by which H2S elicits neuroprotective effects in the progression of Parkinson's disease (PD) remains unclear. To investigate the role of H2S in delaying the pathological process of PD, we used the most common sodium hydrosulfide (NaHS) as an H2S donor and established a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) in the present study. Our results show that H2S reduced neuronal loss during the progression of PD. Notably, we found that H2S exhibited protective effects on dopaminergic neurons. Excitingly, H2S also increased the proliferation of neural stem cells in the subventricular zone. Next, we evaluated whether the neuroprotective effects of H2S on dopaminergic neurons in PD are dependent on adult nerve regeneration by treating primary adult neural stem cells cultured ex vivo with 1-methyl-4-phenylpyridine. Our results show that H2S could prevent nerve injury induced by 1-methyl-4-phenylpyridine, promote the growth of neurospheres, and promote neurogenesis by regulating Akt/glycogen synthase kinase-3β/β-catenin pathways in adult neural stem cells. These findings confirm that H2S can increase neurogenesis in an adult mouse model of PD by regulating the Akt/glycogen synthase kinase-3β/β-catenin signaling pathway. This study was approved by the Animal Care and Use Committee of Nanjing Medical University, China (IACUC Approval No. 1601153-3).