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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).

SUBMITTER: Wang M

PROVIDER: S-EPMC8284305 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Fish are a convenient model for the study of reparative and post-traumatic processes of central nervous system (CNS) recovery, because the formation of new cells in their CNS continues throughout life. After a traumatic injury to the cerebellum of juvenile masu salmon, Oncorhynchus masou, the cell composition of the neurogenic zones containing neural stem cells (NSCs)/neural progenitor cells (NPCs) in the acute period (two days post-injury) changes. The presence of neuroepithelial (NE) and radial glial (RG) neuronal precursors located in the dorsal, lateral, and basal zones of the cerebellar body was shown by the immunohistochemical (IHC) labeling of glutamine synthetase (GS). Progenitors of both types are sources of neurons in the cerebellum of juvenile O. masou during constitutive growth, thus, playing an important role in CNS homeostasis and neuronal plasticity during ontogenesis. Precursors with the RG phenotype were found in the same regions of the molecular layer as part of heterogeneous constitutive neurogenic niches. The presence of neuroepithelial and radial glia GS+ cells indicates a certain proportion of embryonic and adult progenitors and, obviously, different contributions of these cells to constitutive and reparative neurogenesis in the acute post-traumatic period. Expression of nestin and vimentin was revealed in neuroepithelial cerebellar progenitors of juvenile O. masou. Patterns of granular expression of these markers were found in neurogenic niches and adjacent areas, which probably indicates the neurotrophic and proneurogenic effects of vimentin and nestin in constitutive and post-traumatic neurogenesis and a high level of constructive metabolism. No expression of vimentin and nestin was detected in the cerebellar RG of juvenile O. masou. Thus, the molecular markers of NSCs/NPCs in the cerebellum of juvenile O. masou are as follows: vimentin, nestin, and glutamine synthetase label NE cells in intact animals and in the post-traumatic period, while GS expression is present in the RG of intact animals and decreases in the acute post-traumatic period. A study of distribution of cystathionine β-synthase (CBS) in the cerebellum of intact young O. masou showed the expression of the marker mainly in type 1 cells, corresponding to NSCs/NCPs for other molecular markers. In the post-traumatic period, the number of CBS+ cells sharply increased, which indicates the involvement of H2S in the post-traumatic response. Induction of CBS in type 3 cells indicates the involvement of H2S in the metabolism of extracellular glutamate in the cerebellum, a decrease in the production of reactive oxygen species, and also arrest of the oxidative stress development, a weakening of the toxic effects of glutamate, and a reduction in excitotoxicity. The obtained results allow us to consider H2S as a biologically active substance, the numerous known effects of which can be supplemented by participation in the processes of constitutive neurogenesis and neuronal regeneration.

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

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