中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (5): 786-791.doi: 10.4103/1673-5374.156978

• 原著:退行性病与再生 • 上一篇    下一篇

MicroRNA-124可促进纹状体神经发生:延缓亨廷顿病的进展

  

  • 收稿日期:2015-02-16 出版日期:2015-05-15 发布日期:2015-05-15
  • 基金资助:

    韩国健康福利部健康技术R&D项目(A121911 and HI14C2348);韩国国家研究基金 (2011-0012728 and 2014R1A2A1A11051520)

MicroRNA-124 slows down the progression of Huntington’s disease by promoting neurogenesis in the striatum

Tian Liu 1, Wooseok Im 2, Inhee Mook-Jung 1, 3, Manho Kim 2, 4   

  1. 1 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea
    2 Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea
    3 Department of Biochemistry, Seoul National University College of Medicine, Seoul, South Korea
    4 Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, Seoul, South Korea
  • Received:2015-02-16 Online:2015-05-15 Published:2015-05-15
  • Contact: Manho Kim, M.D., Ph.D., kimmanho@snu.ac.kr
  • Supported by:

    This study was supported by a grant (A121911 and HI14C2348) of the Korean Health Technology R&D Project, Ministry of Health & Welfare, and National Research Foundation of Korea (NRF) (2011-0012728 and 2014R1A2A1A11051520).

摘要:

microRNA-124利于神经发生,但亨廷顿病模型小鼠和患者大脑microRNA-124表达均降低。microRNA-124对亨廷顿病病程的影响尚未见报道。实验发现microRNA-124使R6/2亨廷顿病转基因小鼠在疲劳转棒试验中的下落潜伏期延长。纹状体BrdU染色显示,神经发生增强。同时,纹状体脑源性神经营养因子和过氧化物酶体增殖物受体γ共激活因子1α蛋白表达明显上升,而SRY 盒转录因子9蛋白表达下降,说明microRNA-124可能在神经元的分化和存活中有重要作用。microRNA-124正是通过上述途径起到延缓亨廷顿病病程进展的作用。

关键词: 神经再生, microRNA-124, 神经发生, 神经元存活, 亨廷顿病, SOX9, BDNF, PGC1, 突变亨廷顿蛋白

Abstract:

MicroRNA-124 contributes to neurogenesis through regulating its targets, but its expression both in the brain of Huntington’s disease mouse models and patients is decreased. However, the effects of microRNA-124 on the progression of Huntington’s disease have not been reported. Results from this study showed that microRNA-124 increased the latency to fall for each R6/2 Huntington’s disease transgenic mouse in the rotarod test. 5-Bromo-2’-deoxyuridine (BrdU) staining of the striatum shows an increase in neurogenesis. In addition, brain-derived neurotrophic factor and peroxisome proliferator-activated receptor gamma coactivator 1-alpha protein levels in the striatum were increased and SRY-related HMG box transcription factor 9 protein level was decreased. These findings suggest that microRNA-124 slows down the progression of Huntington’s disease possibly through its important role in neuronal differentiation and survival.