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Hippocampal miRNA-144 Modulates Depressive-Like Behaviors in Rats by Targeting PTP1B

Authors Li Y, Wang N, Pan J, Wang X, Zhao Y, Guo Z

Received 3 June 2020

Accepted for publication 16 November 2020

Published 10 February 2021 Volume 2021:17 Pages 389—399

DOI https://doi.org/10.2147/NDT.S263079

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Jun Chen


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 China

Correspondence: Xinrui Wang
Department of Psychology, Qingdao Mental Health Center, No. 9 Dong ‘an Road, North District, Qingdao City, Shandong Province, 266000, People’s Republic of China
Tel +86 532-8093158
Email ffssmh256766237@126.com

Background: 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

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