中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (26): 2441-2448.doi: 10.3969/j.issn.1673-5374.2013.26.005

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

miR-137可是卒中后抑郁治疗治疗的新靶点？

  

  • 收稿日期:2013-03-15 修回日期:2013-07-11 出版日期:2013-09-15 发布日期:2013-09-15

miR-137, a new target for post-stroke depression?

Lixia Zhao1, 2, Huazi Li3, Ruiyou Guo2, Teng Ma2, Rongyao Hou2, Xiaowei Ma2, Yifeng Du1   

  1. 1 Department of Neurology, Shandong Provincial Hospital, Jinan 250021, Shandong Province, China

    2 Department of Neurology, Haici Hospital Affiliated to Medical College of Qingdao University, Qingdao 266033, Shandong Province, China

    3 Department of Medical Imaging, Haici Hospital Affiliated to Medical College of Qingdao University, Qingdao 266033, Shandong Province, China
  • Received:2013-03-15 Revised:2013-07-11 Online:2013-09-15 Published:2013-09-15
  • Contact: Yifeng Du, M.D., Chief physician, Department of Neurology, Shandong Provincial Hospital, Jinan 250021, Shandong Province, China, zhaolixia1313@126.com.
  • About author:Lixia Zhao, M.D., Attending physician.

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摘要：

既往研究发现miR-137在抑郁自杀患者的脑组织中表达下调，且对脑卒中患者外周血检测发现miR-137表达水平也下调，那么miR-137是否起到联系卒中和抑郁的桥梁作用呢？为验证上述构想，实验采用大脑中动脉阻塞法结合慢性温和刺激法制作卒中后抑郁模型，发现在卒中后抑郁大鼠模型脑内和外周血中的miR-137水平较正常大鼠明显下降；通过脑室注射miR-137激动剂上调脑内miR-137水平后，卒中后抑郁大鼠模型的行为学变化可显著改善。通过luciferase assay检测发现 miR-137可以与Grin2A的3’UTR端结合，并且在神经细胞系中miR-137可以调控Grin2A的表达。在卒中后抑郁大鼠模型的脑内过表达Grin2A基因后，miR-137抗卒中后抑郁的作用被显著减弱。提示miR-137可通过与Grin2A mRNA结合抑制其蛋白表达，从而发挥抗卒中后抑郁的作用，这一结果提示卒中后抑郁新的治疗方向。

关键词: 神经再生, 脑损伤, 卒中后抑郁, microRNA, 脑血管病, Grin2A, miR-137 

Abstract:

Expression of miR-137 is downregulated in brain tissue from patients with depression and suicidal behavior, and is also downregulated in peripheral blood from stroke patients. However, it is not yet known if miR-137 acts as a bridge between stroke and depression. To test this, we used middle cerebral artery occlusion and chronic mild stress to establish a post-stroke depression model in rats. Compared with controls, we found significantly lower miR-137 levels in the brain and peripheral blood from post-stroke depression rats. Injection of a miR-137 antagonist into the brain ventricles upregulated miR-137 levels, and improved behavioral changes in post-stroke depression rats. Lu-ciferase assays showed miR-137 bound to the 3′UTR of Grin2A, regulating Grin2A expression in a neuronal cell line. Grin2A gene overexpression in the brain of post-stroke depression rats, noticea-bly suppressed the inhibitory effect of miR-137 on post-stroke depression. Overall, our results show that miR-137 suppresses Grin2A protein expression through binding to Grin2A mRNA, thereby ex-erting an inhibitory effect on post-stroke depression. Our results offer a new therapeutic direction for post-stroke depression.

Key words: neural regeneration, brain injury, post-stroke depression, microRNA, cerebrovascular disease, Grin2A, miR-137, neuroregeneration