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

Hydrogen sulfide (H(2)S) is regarded to be a protectant against diseases of the central nervous system and cardiovascular system. However, the mechanism by which H(2)S elicits neuroprotective effects in the progression of Parkinson’s disease (PD) remains unclear. To investigate the role of H(2)S in delaying the pathological process of PD, we used the most common sodium hydrosulfide (NaHS) as an H(2)S 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 H(2)S reduced neuronal loss during the progression of PD. Notably, we found that H(2)S exhibited protective effects on dopaminergic neurons. Excitingly, H(2)S also increased the proliferation of neural stem cells in the subventricular zone. Next, we evaluated whether the neuroprotective effects of H(2)S 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 H(2)S 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 H(2)S 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).