Neuropsychiatric Disease and Treatment (Feb 2021)
Hippocampal miRNA-144 Modulates Depressive-Like Behaviors in Rats by Targeting PTP1B
Abstract
Yuhuan Li,1 Nina Wang,2 Jie Pan,2 Xinrui Wang,1 Yanling Zhao,3 Zongjun Guo4 1Department of Psychology, Qingdao Mental Health Center, Qingdao City, Shandong Province, 266000, People’s Republic of China; 2Department of Pharmacy, Qingdao Mental Health Center, Qingdao City, Shandong Province, 266000, People’s Republic of China; 3Department of Methadone Clinic, Qingdao Mental Health Center, Qingdao City, Shandong Province, 266000, People’s Republic of China; 4Department of Geriatric Internal Medicine, The Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province, 266000, People’s Republic of ChinaCorrespondence: Xinrui WangDepartment of Psychology, Qingdao Mental Health Center, No. 9 Dong ‘an Road, North District, Qingdao City, Shandong Province, 266000, People’s Republic of ChinaTel +86 532-8093158Email [email protected]: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: miR-144, CUMS, hippocampus, PTP1B, TrkB/BDNF
