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Hippocampal BAIAP2 prevents chronic mild stress-induced depression-like behaviors in mice
BACKGROUND: The pathogenesis of depression is closely related to changes in hippocampal synaptic plasticity; however, the underlying mechanism is still unclear. Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2), a postsynaptic scaffold protein in excitatory synapses important for...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10206043/ https://www.ncbi.nlm.nih.gov/pubmed/37234209 http://dx.doi.org/10.3389/fpsyt.2023.1192379 |
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author | Fu, Yaling Guo, Xiangfei Yang, Rui Feng, Hao Yin, Xueyong Wang, Shuang Song, Li Wang, Xi Zhao, Penghui Wang, Sheng Shi, Yun Shi, Haishui |
author_facet | Fu, Yaling Guo, Xiangfei Yang, Rui Feng, Hao Yin, Xueyong Wang, Shuang Song, Li Wang, Xi Zhao, Penghui Wang, Sheng Shi, Yun Shi, Haishui |
author_sort | Fu, Yaling |
collection | PubMed |
description | BACKGROUND: The pathogenesis of depression is closely related to changes in hippocampal synaptic plasticity; however, the underlying mechanism is still unclear. Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2), a postsynaptic scaffold protein in excitatory synapses important for synaptic plasticity, is highly expressed in the hippocampus and has been implicated in several psychiatric disorders. However, the role of BAIAP2 in depression remains poorly understood. METHODS: In the present study, a mouse model of depression was established via exposure to chronic mild stress (CMS). An adeno-associated virus (AAV) vector expressing BAIAP2 was injected into the hippocampal brain region of mice and a BAIAP2 overexpression plasmid was transfected into HT22 cells to upregulate BAIAP2 expression. Depression- and anxiety-like behaviors and dendritic spine density were examined in mice using behavioral tests and Golgi staining, respectively. In vitro, hippocampal HT22 cells were treated with corticosterone (CORT) to simulate the stress state, and the effect of BAIAP2 on CORT-induced cell injury was explored. Reverse transcription-quantitative PCR and western blotting were employed to determine the expression levels of BAIAP2 and those of the synaptic plasticity-related proteins glutamate receptor ionotropic, AMPA 1 (GluA1), and synapsin 1 (SYN1). RESULTS: Mice exposed to CMS exhibited depression- and anxiety-like behaviors accompanied by decreased levels of BAIAP2 in the hippocampus. In vitro, the overexpression of BAIAP2 increased the survival rate of CORT-treated HT22 cells and upregulated the expression of GluA1 and SYN1. Consistent with the in vitro data, the AAV-mediated overexpression of BAIAP2 in the hippocampus of mice significantly inhibited CMS-induced depression-like behavior, concomitant with increases in dendritic spine density and the expression of GluA1 and SYN1 in hippocampal regions. CONCLUSION: Our findings indicate that hippocampal BAIAP2 can prevent stress-induced depression-like behavior and may be a promising target for the treatment of depression or other stress-related diseases. |
format | Online Article Text |
id | pubmed-10206043 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102060432023-05-25 Hippocampal BAIAP2 prevents chronic mild stress-induced depression-like behaviors in mice Fu, Yaling Guo, Xiangfei Yang, Rui Feng, Hao Yin, Xueyong Wang, Shuang Song, Li Wang, Xi Zhao, Penghui Wang, Sheng Shi, Yun Shi, Haishui Front Psychiatry Psychiatry BACKGROUND: The pathogenesis of depression is closely related to changes in hippocampal synaptic plasticity; however, the underlying mechanism is still unclear. Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2), a postsynaptic scaffold protein in excitatory synapses important for synaptic plasticity, is highly expressed in the hippocampus and has been implicated in several psychiatric disorders. However, the role of BAIAP2 in depression remains poorly understood. METHODS: In the present study, a mouse model of depression was established via exposure to chronic mild stress (CMS). An adeno-associated virus (AAV) vector expressing BAIAP2 was injected into the hippocampal brain region of mice and a BAIAP2 overexpression plasmid was transfected into HT22 cells to upregulate BAIAP2 expression. Depression- and anxiety-like behaviors and dendritic spine density were examined in mice using behavioral tests and Golgi staining, respectively. In vitro, hippocampal HT22 cells were treated with corticosterone (CORT) to simulate the stress state, and the effect of BAIAP2 on CORT-induced cell injury was explored. Reverse transcription-quantitative PCR and western blotting were employed to determine the expression levels of BAIAP2 and those of the synaptic plasticity-related proteins glutamate receptor ionotropic, AMPA 1 (GluA1), and synapsin 1 (SYN1). RESULTS: Mice exposed to CMS exhibited depression- and anxiety-like behaviors accompanied by decreased levels of BAIAP2 in the hippocampus. In vitro, the overexpression of BAIAP2 increased the survival rate of CORT-treated HT22 cells and upregulated the expression of GluA1 and SYN1. Consistent with the in vitro data, the AAV-mediated overexpression of BAIAP2 in the hippocampus of mice significantly inhibited CMS-induced depression-like behavior, concomitant with increases in dendritic spine density and the expression of GluA1 and SYN1 in hippocampal regions. CONCLUSION: Our findings indicate that hippocampal BAIAP2 can prevent stress-induced depression-like behavior and may be a promising target for the treatment of depression or other stress-related diseases. Frontiers Media S.A. 2023-05-10 /pmc/articles/PMC10206043/ /pubmed/37234209 http://dx.doi.org/10.3389/fpsyt.2023.1192379 Text en Copyright © 2023 Fu, Guo, Yang, Feng, Yin, Wang, Song, Wang, Zhao, Wang, Shi and Shi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Psychiatry Fu, Yaling Guo, Xiangfei Yang, Rui Feng, Hao Yin, Xueyong Wang, Shuang Song, Li Wang, Xi Zhao, Penghui Wang, Sheng Shi, Yun Shi, Haishui Hippocampal BAIAP2 prevents chronic mild stress-induced depression-like behaviors in mice |
title | Hippocampal BAIAP2 prevents chronic mild stress-induced depression-like behaviors in mice |
title_full | Hippocampal BAIAP2 prevents chronic mild stress-induced depression-like behaviors in mice |
title_fullStr | Hippocampal BAIAP2 prevents chronic mild stress-induced depression-like behaviors in mice |
title_full_unstemmed | Hippocampal BAIAP2 prevents chronic mild stress-induced depression-like behaviors in mice |
title_short | Hippocampal BAIAP2 prevents chronic mild stress-induced depression-like behaviors in mice |
title_sort | hippocampal baiap2 prevents chronic mild stress-induced depression-like behaviors in mice |
topic | Psychiatry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10206043/ https://www.ncbi.nlm.nih.gov/pubmed/37234209 http://dx.doi.org/10.3389/fpsyt.2023.1192379 |
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