中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (10): 1079-1088.doi: 10.4103/1673-5374.133171

• 原著:退行性病与再生 • 上一篇    

中型多棘神经元膜兴奋性抑制作用减弱:可能参与幼年期抑郁症发病?

  

  • 收稿日期:2014-04-11 出版日期:2014-05-26 发布日期:2014-05-26
  • 基金资助:

    国家自然科学基金(31271198,81121001), 上海科学技术委员会项目(11zr1415900),复旦大学医学神经生物学国家重点实验室项目(10–12)

Attenuated inhibition of medium spiny neurons participates in the pathogenesis of childhood depression

Dandan Liu, Linghan Hu, Junqi Zhang, Ping Zhang, Shengtian Li   

  1. Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
  • Received:2014-04-11 Online:2014-05-26 Published:2014-05-26
  • Contact: Shengtian Li, M.D., Ph.D., Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200240, China, lstian@sjtu.edu.cn.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 31271198 and 81121001; grants from the Shanghai Committee of Science and Technology, No. 11ZR1415900; and the State Key Laboratory of Medical Neurobiology, Fudan University, No. 10-12.

摘要:

许多证据提示,负责奖赏及成瘾机制的重要脑区伏隔核在抑郁发病及抗抑郁药物治疗中发挥着重要的作用。我们的实验结果显示,用多巴胺重摄取抑制剂诺米芬辛腹腔注射能够降低抑郁症模型WKY大鼠在糖水偏好实验和强迫游泳实验中的抑郁样行为程度,还可以降低其伏隔核脑区中心区域中型多棘神经元膜的兴奋性,接受诺米芬辛治疗的模型大鼠的伏隔核、纹状体和海马区多巴胺D2型受体mRNA表达均不同程度上调。说明伏隔核区域多巴胺D2型受体介导的中型多棘神经元膜兴奋性抑制作用的减弱可能参与幼年期模型大鼠抑郁样行为的发生,并且诺米芬辛通过对中型多棘神经元膜兴奋性的抑制可改善抑郁样行为。

关键词: 神经再生, 脑损伤, 神经生理学, 中型多棘神经元, 多巴胺2类受体, 幼年期抑郁症, WKY大鼠, 伏隔核, 兴奋性抑制, 神经可塑性, 诺米芬辛, 国家自然科学基金

Abstract:

Accumulating evidence suggests that the nucleus accumbens, which is involved in mechanisms of reward and addiction, plays a role in the pathogenesis of depression and in the action of antidepressants. In the current study, intraperitoneal injection of nomifensine, a dopamine reuptake inhibitor, decreased depression-like behaviors in the Wistar Kyoto rat model of depression in the sucrose-preference and forced swim tests. Nomifensine also reduced membrane excitability in medium spiny neurons in the core of the nucleus accumbens in the childhood Wistar Kyoto rats as evaluated by electrophysiological recording. In addition, the expression of dopamine D2-like receptor mRNA was downregulated in the nucleus accumbens, striatum and hippocampus of nomifensine-treated childhood Wistar Kyoto rats. These experimental findings indicate that impaired inhibition of medium spiny neurons, mediated by dopamine D2-like receptors, may be involved in the formation of depression-like behavior in childhood Wistar Kyoto rats, and that nomifensine can alleviate depressive behaviors by reducing medium spiny neuron membrane excitability.

Key words: nerve regeneration, brain injury, neurophysiology, MSNs, dopamine D2-like receptors, childhood depression, Wistar Kyoto rats, nucleus accumbens, excitatory inhibition, neural plasticity, nomifensine, NSFC grant, neural regeneration