Li Yuhuan, Wang Nina, Pan Jie, Wang Xinrui, Zhao Yanling, Guo Zongjun
Department of Psychology, Qingdao Mental Health Center, Qingdao City, Shandong Province, 266000, People's Republic of China.
Department of Pharmacy, Qingdao Mental Health Center, Qingdao City, Shandong Province, 266000, People's Republic of China.
Neuropsychiatr Dis Treat. 2021 Feb 10;17:389-399. doi: 10.2147/NDT.S263079. eCollection 2021.
Depression is the common mental disorder in the world. However, the pathophysiology mechanism underlying depression remains elusive. It has been reported that aberrant expression of miR-144 is closely related to depression. This study was to investigate whether and how miR-144 involves in depressive-like behaviors in a chronic unpredictable mild stress (CUMS) animal model.
A rat model of CUMS was established, and qRT-PCR was performed to detect the expression of miR-144 in the hippocampus of a depressed rat. The lentiviral vector carried miR-144 (LV-miR-144) was injected into the hippocampus of the CUMS rat to investigate the effects of miR-144 on the behaviors and PTP1B/TrkB/BDNF signal transduction in the hippocampus of the rat. The interaction between miR-144 and PTP1B was investigated by biological analyses and dual-luciferase reporter assay.
The results showed that CUMS rats had typical depressive behaviors, and the expression of miR-144 in the hippocampus of CUMS rats was significantly lower than that of the control group. In addition, PTP1B protein expression was significantly up-regulated, while the expression of pTrkB and BDNF protein was significantly down-regulated in the hippocampus of CUMS rats. Moreover, PTP1B was a direct target of miR-144, and miR-144 could activate the downstream TrkB/BDNF signaling pathway by inhibiting the expression of PTP1B in primary hippocampus neurons.
MiR-144 played an anti-depressive role in hippocampus dysfunction by inhibiting PTP1B and activating the TrkB/BDNF signaling pathway in the hippocampus of CUMS rats.
抑郁症是全球常见的精神障碍。然而，抑郁症潜在的病理生理机制仍不清楚。据报道，miR-144的异常表达与抑郁症密切相关。本研究旨在探讨miR-144是否以及如何参与慢性不可预测性温和应激（CUMS）动物模型中的抑郁样行为。
建立CUMS大鼠模型，采用qRT-PCR检测抑郁大鼠海马中miR-144的表达。将携带miR-144的慢病毒载体（LV-miR-144）注射到CUMS大鼠的海马中，以研究miR-144对大鼠海马行为及PTP1B/TrkB/BDNF信号转导的影响。通过生物学分析和双荧光素酶报告基因检测研究miR-144与PTP1B之间的相互作用。
结果显示，CUMS大鼠表现出典型的抑郁行为，且CUMS大鼠海马中miR-144的表达明显低于对照组。此外，CUMS大鼠海马中PTP1B蛋白表达显著上调，而pTrkB和BDNF蛋白表达显著下调。而且，PTP1B是miR-144的直接靶点，miR-144可通过抑制原代海马神经元中PTP1B的表达来激活下游TrkB/BDNF信号通路。
在CUMS大鼠海马中，miR-144通过抑制PTP1B并激活TrkB/BDNF信号通路，在海马功能障碍中发挥抗抑郁作用。
