中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (21): 1917-1922.doi: 10.4103/1673-5374.145361

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

抑制Sirtuin 2可减少幼时摄入高铁大鼠衰老后纹状体神经元多巴胺耗竭

  

  • 收稿日期:2014-09-28 出版日期:2014-11-15 发布日期:2014-11-15
  • 基金资助:

    国家自然科学基金项目（81171204，81171203，30772280，81200871，81200921），上海市教委基金项目（14YZ046），上海市卫生和计划生育委员会基金项目（20134049），上海交通大学基金项目（YG2013MS22），上海科技委基金项目（11nm0503300，12XD1403800）

Inhibition of Sirtuin 2 exerts neuroprotection in aging rats with increased neonatal iron intake

Xijin Wang 1, Meihua Wang 1, Liu Yang 1, Jie Bai 1, Zhiqiang Yan 2, Yuhong Zhang 3, Zhenguo Liu 1   

  1. 1 Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
    2 Shanghai Laboratory Animal Center, Chinese Academy of Sciences, Shanghai, China
    3 Department of Neurology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China
  • Received:2014-09-28 Online:2014-11-15 Published:2014-11-15
  • Contact: Zhenguo Liu, M.D., Ph.D., Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China, zhenguoliu2004@aliyun.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81171204, 81171203, 30772280, 81200871, and 81200921; a grant from the Project of Shanghai Municipal Education Commission of China, No. 14YZ046; a grant from the Project of Shanghai Municipal Health and Family Planning Commission of China, No. 20134049; a grant from the Project of Shanghai Jiao Tong University of China, No. YG2013MS22; and a grant from the Projects of Shanghai Committee of Science and Technology of China, No. 11nm0503300 and 12XD1403800.

PDF

678

摘要：

铁代谢受损可能损害多巴胺能神经元，与帕金森病的发病机制有关。目前，还较少有关于新生儿铁干预对衰老动物行为的研究。因此，实验假设增加幼时高铁摄入可导致与衰老有关的行为异常和纹状体神经元多巴胺耗竭，且Sirtuin 2可能参与衰老相关的神经毒性。我们观察到在出生后10-17d接受高铁(120 µg/g/d)灌胃的大鼠，衰老后出现明显的纹状体神经元多巴胺耗竭和行为异常。在出生后540d和570d双侧黑质内分别注射5µg/d的Sirtuin 2抑制剂AK-7可显著改善幼时高铁摄入的衰老大鼠纹状体神经元中多巴胺耗竭及行为异常。表明大鼠幼时高铁摄入会导致衰老后出现帕金森病样的神经化学和行为变化，而抑制Sirtuin 2表达可以对其产生神经保护作用。

关键词: 神经再生, 帕金森病, 铁失衡, 年龄, 衰老, 多巴胺, 纹状体, 神经毒性, Sirtuin 2, AK-7

Abstract:

Impaired iron homeostasis may cause damage to dopaminergic neurons and is critically involved in the pathogenesis of Parkinson’s disease. At present, very little is understood about the effect of neonatal iron intake on behavior in aging animals. Therefore, we hypothesized that increased neonatal iron intake would result in significant behavior abnormalities and striatal dopamine depletion during aging, and Sirtuin 2 contributes to the age-related neurotoxicity. In the present study, we observed that neonatal iron intake (120 µg/g per day) during postnatal days 10–17 resulted in significant behavior abnormalities and striatal dopamine depletion in aging rats. Furthermore, after AK-7 (a selective Sirtuin 2 inhibitor) was injected into the substantia nigra at postnatal 540 days and 570 days (5 µg/side per day), striatal dopamine depletion was significantly diminished and behavior abnormality was improved in aging rats with neonatal iron intake. Experimental findings suggest that increased neonatal iron intake may result in Parkinson’s disease-like neurochemical and behavioral deficits with aging, and inhibition of Sirtuin 2 expression may be a neuroprotective measure in Parkinson’s disease.

Key words: nerve regeneration, Parkinson’s disease, iron homeostasis disruption, aging, dopamine, corpus striatum, neurotoxicity, Sirtuin, AK-7, NSFC grants, neural regeneration