Ruan Chun-Sheng, Wang Shu-Fen, Shen Yan-Jun, Guo Yi, Yang Chun-Rui, Zhou Fiona H, Tan Li-Tao, Zhou Li, Liu Jian-Jun, Wang Wen-Yue, Xiao Zhi-Cheng, Zhou Xin-Fu
Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, China; Division of Health Sciences, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia.
Eur J Neurosci. 2014 Aug;40(4):2680-90. doi: 10.1111/ejn.12618. Epub 2014 May 20.
Chronic stress causes a variety of psychiatric disorders such as anxiety and depression, but its mechanism is not well understood. Tripartite motif-containing protein 32 (TRIM32) was strongly associated with autism spectrum disorder, attention deficit hyperactivity disorder, anxiety and obsessive compulsive disorder based on a study of copy number variation, and deletion of TRIM32 increased neural proliferation and reduced apoptosis. Here, we propose that TRIM32 is involved in chronic stress-induced affective behaviors. Using a chronic unpredictable mild stress mouse depression model, we studied expression of TRIM32 in brain tissue samples and observed behavioral changes in Trim32 knockout mice. The results showed that TRIM32 protein but not its mRNA was significantly reduced in hippocampus in a time-dependent manner within 8 weeks of chronic stress. These stress-induced affective behaviors and reduction of TRIM32 protein expression were significantly reversed by antidepressant fluoxetine treatment. In addition, Trim32 knockout mice showed reduced anxiety and depressive behaviors and hyperactivities compared with Trim32 wild-type mice under normal and mild stress conditions. We conclude that TRIM32 plays important roles in regulation of hyperactivities and positively regulates the development of anxiety and depression disorders induced by chronic stress.
慢性应激会引发多种精神疾病，如焦虑症和抑郁症，但其机制尚未完全明确。基于一项拷贝数变异研究，含三联基序蛋白32（TRIM32）与自闭症谱系障碍、注意力缺陷多动障碍、焦虑症和强迫症密切相关，且TRIM32缺失会增加神经增殖并减少细胞凋亡。在此，我们提出TRIM32参与慢性应激诱导的情感行为。利用慢性不可预测温和应激小鼠抑郁模型，我们研究了TRIM32在脑组织样本中的表达，并观察了Trim32基因敲除小鼠的行为变化。结果显示，在慢性应激8周内，海马体中TRIM32蛋白而非其mRNA呈时间依赖性显著减少。抗抑郁药氟西汀治疗可显著逆转这些应激诱导的情感行为以及TRIM32蛋白表达的降低。此外，在正常和轻度应激条件下，与Trim32野生型小鼠相比，Trim32基因敲除小鼠的焦虑和抑郁行为以及多动行为减少。我们得出结论，TRIM32在多动调节中起重要作用，并正向调节慢性应激诱导的焦虑和抑郁障碍的发展。
