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MAD2B Blunts Chronic Unpredictable Stress and Corticosterone Stimulation–Induced Depression-Like Behaviors in Mice
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926055/ https://www.ncbi.nlm.nih.gov/pubmed/36573299 http://dx.doi.org/10.1093/ijnp/pyac083 |
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author | Wang, Xiao-Lan Miao, Cheng Su, Yanfang Zhang, Chun Meng, Xianfang |
author_facet | Wang, Xiao-Lan Miao, Cheng Su, Yanfang Zhang, Chun Meng, Xianfang |
author_sort | Wang, Xiao-Lan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9926055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-99260552023-02-14 MAD2B Blunts Chronic Unpredictable Stress and Corticosterone Stimulation–Induced Depression-Like Behaviors in Mice Wang, Xiao-Lan Miao, Cheng Su, Yanfang Zhang, Chun Meng, Xianfang Int J Neuropsychopharmacol Regular Research Articles 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. Oxford University Press 2022-12-27 /pmc/articles/PMC9926055/ /pubmed/36573299 http://dx.doi.org/10.1093/ijnp/pyac083 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of CINP. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Regular Research Articles Wang, Xiao-Lan Miao, Cheng Su, Yanfang Zhang, Chun Meng, Xianfang MAD2B Blunts Chronic Unpredictable Stress and Corticosterone Stimulation–Induced Depression-Like Behaviors in Mice |
title | MAD2B Blunts Chronic Unpredictable Stress and Corticosterone Stimulation–Induced Depression-Like Behaviors in Mice |
title_full | MAD2B Blunts Chronic Unpredictable Stress and Corticosterone Stimulation–Induced Depression-Like Behaviors in Mice |
title_fullStr | MAD2B Blunts Chronic Unpredictable Stress and Corticosterone Stimulation–Induced Depression-Like Behaviors in Mice |
title_full_unstemmed | MAD2B Blunts Chronic Unpredictable Stress and Corticosterone Stimulation–Induced Depression-Like Behaviors in Mice |
title_short | MAD2B Blunts Chronic Unpredictable Stress and Corticosterone Stimulation–Induced Depression-Like Behaviors in Mice |
title_sort | mad2b blunts chronic unpredictable stress and corticosterone stimulation–induced depression-like behaviors in mice |
topic | Regular Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926055/ https://www.ncbi.nlm.nih.gov/pubmed/36573299 http://dx.doi.org/10.1093/ijnp/pyac083 |
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