中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (7): 1353-1358.doi: 10.4103/1673-5374.301026

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

硫化氢可增强帕金森病小鼠模型的成年神经发生

  

  • 出版日期:2021-07-15 发布日期:2021-01-07
  • 基金资助:

    国家自然科学基金面上项目(8180350581803498);江苏省自然科学基金项目(BK20170564);江苏大学人才培养计划(5521470000

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

Min Wang2, #, Juan-Juan Tang3, #, Lin-Xiao Wang4, Jun Yu5, Li Zhang2, *, Chen Qiao1, *   

  1. 1 Department of Clinical Pharmacy, The Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu Province, China;  2 Department of Geriatrics, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China;  3 School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China; 4 Laboratory of Neurological Diseases, Department of Neurology, the Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China;  5 Laboratory of Reproductive Medicine, The Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu Province, China
  • Online:2021-07-15 Published:2021-01-07
  • Contact: Chen Qiao, MD, PhD, qiaochennjmu@126.com; Li Zhang, MD, PhD, neuro_zhangli@163.com.
  • Supported by:
    The study was supported by the National Natural Science Foundation of China, Nos. 81803505 (to CQ), 81803498 (to LXW); the Natural Science Foundation of Jiangsu Province of China, No. BK20170564 (to CQ), and Yong Talents Training Program of Jiangsu University of China, No. 5521470000 (to JY).

摘要:

既往研究显示,硫化氢(H2S)可作为中枢神经系统和心血管系统疾病的保护剂;然而,H2S在帕金森病进展中发挥神经保护作用的确切机制尚不清楚。实验以最常用的NaHS作为H2S的供体,并建立了经典的1-甲基-4-苯基-1,2,3,6 -四氢吡啶/丙磺舒诱导的帕金森病小鼠模型,观察H2S在延缓帕金森病病理进展中的作用。发现H2S可减少帕金森病进展过程中的神经元丢失的现象,尤其是对多巴胺能神经元具有确切的保护作用。令人兴奋的是,H2S还会增加帕金森病模型小鼠侧脑室下区神经干细胞的增殖。紧接着,给予离体培养的原代成年小鼠神经干细胞1-甲基-4-苯基吡啶刺激,以阐明H2S对帕金森病中多巴胺能神经元的保护作用是否依赖于成年神经再生。结果发现H2S可抵御1-甲基-4-苯基吡啶造成的神经损伤,促进神经干细胞球的生长,并通过调控成年神经干细胞中Akt/糖原合成酶激酶3β/β-连环蛋白信号通路发挥促神经再生作用。实验结果证实硫化氢增强帕金森病小鼠模型的成年神经发生,且其作用是通过调节Akt/糖原合成酶激酶3β/β-连环蛋白信号通路实现的。实验于201686日经南京医科大学动物委员会批准,批准号:IACUC1601153-3

https://orcid.org/0000-0003-4315-0351 (Chen Qiao)

关键词: 神经保护, 神经发生, 神经干细胞, 帕金森病, 医用气体, 硫化氢, 因子, 通路

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). 

Key words: factor, hydrogen sulfide, medical gas, neural stem cells, neurogenesis, neuroprotection, Parkinson’s disease, pathways