Hippocampal miRNA-144 Modulates Depressive-Like Behaviors in Rats by Targeting PTP1B
Authors: Jie Pan
Yuhuan Li
Zongjun Guo
Nina Wang
Xinrui Wang
Yanling Zhao
Journal: Neuropsychiatric Disease and Treatment (2021)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: CUMS; PTP1B; TrkB/BDNF; hippocampus; miR-144.
Affiliations: 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., Department of Methadone Clinic, Qingdao Mental Health Center, Qingdao City, Shandong Province, 266000, People's Republic of China., Department of Geriatric Internal Medicine, The Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province, 266000, People's Republic of China.

Abstract:  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. 

Retracted: No

PubPeer comments:
 Would the authors provide an explanation for the apparent similarities between the two following FACS panels in Figure 2B, which corresponded to the different experimental conditions? The colored circles and arrows show areas with unexpected similarities. ![file] , 
 The same photo has been used in figure 4A and figure S4C. The authors have mentioned that the photo presented in figure 4A and S4C are respectively related to the cells transfected with control vector and the untransfected cells. ![file] , 
 Dear Phrixocomes Ophiucha, Thank you for having read our paper in details. - Regarding the Figure 4A S4C this image refers to the same cells, same staining and the same treatment (treated with a premiR that doesnt target anything). For clarity, we decided at that time to add it in the supplementary figure 4 that provides more details on the same results shown in Fig 4A. - Regarding the FACS I dont have anymore access to the raw datas to check what happened here (it was done 12 years ago). I have done myself these flow cytometry experiments multiple times and everything was done each times in triplicates in several cell types and several cell lines. Have a nice day Xavier ,