MAD2B Blunts Chronic Unpredictable Stress and Corticosterone Stimulation–Induced Depression-Like Behaviors in Mice

Author:

Wang Xiao-Lan12,Miao Cheng2,Su Yanfang2,Zhang Chun1ORCID,Meng Xianfang2

Affiliation:

1. Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China

2. Department of Neurobiology, Institute of Brain Research, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China

Abstract

Abstract Background Depression is a prevalent and recurrent psychiatric disorder. Aberrant neural structure and activity play fundamental roles in the occurrence of depression. Mitotic arrest deficient protein (MAD2B) is highly expressed in neurons and may be implicated in synaptic plasticity in the central nervous system. However, the effect of MAD2B in depression, as well as the related molecular mechanism, is uncertain. Methods Here, we employed mouse models of depression induced by chronic unpredictable stress exposure or corticosterone (CORT) stimulation. Depression-like behaviors in mice were evaluated by sucrose preference, forced swimming, and tail suspension tests. Hippocampal MAD2B overexpression was mediated by adeno-associated virus 8 containing enhanced green fluorescent protein. In vitro primary neuronal cells were obtained from the hippocampus of rat embryos and were treated with CORT, and MAD2B overexpression was performed using lentivirus. MAD2B and glutamate metabotropic receptor 4 (GRM4) levels were evaluated by western blots and quantitative PCR. Primary neuronal miR-29b-3p expression was detected by quantitative PCR. Results MAD2B expression was reduced in the hippocampus in mice exhibiting depressive-like behaviors. However, hippocampal MAD2B overexpression protected mice from developing either chronic unpredictable stress– or CORT-induced depression-like behaviors, an effect associated with reduced expression of GRM4, a presynaptic receptor involved in depression. Moreover, MAD2B overexpression in primary neuronal cells also decreased GRM4 expression while enhancing the level of miR-29b-3p; this phenomenon was also observed under CORT stimulation. Conclusions Our results suggest an important role of neuronal MAD2B in the pathogenesis of depression via the miR-29b-3p/GRM4 signaling pathway. MAD2B could be a potential therapeutic target for depressive disorders.

Funder

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Psychiatry and Mental health,Pharmacology

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