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PTEN in prefrontal cortex is essential in regulating depression-like behaviors in mice
Chronic stress is an environmental risk factor for depression and causes neuronal atrophy in the prefrontal cortex (PFC) and other brain regions. It is still unclear about the molecular mechanism underlying the behavioral alterations and neuronal atrophy induced by chronic stress. We here report tha...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998021/ https://www.ncbi.nlm.nih.gov/pubmed/33771972 http://dx.doi.org/10.1038/s41398-021-01312-y |
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author | Wang, Xiao-Qing Zhang, Lei Xia, Zhong-Yuan Chen, Jia-Yin Fang, Yiru Ding, Yu-Qiang |
author_facet | Wang, Xiao-Qing Zhang, Lei Xia, Zhong-Yuan Chen, Jia-Yin Fang, Yiru Ding, Yu-Qiang |
author_sort | Wang, Xiao-Qing |
collection | PubMed |
description | Chronic stress is an environmental risk factor for depression and causes neuronal atrophy in the prefrontal cortex (PFC) and other brain regions. It is still unclear about the molecular mechanism underlying the behavioral alterations and neuronal atrophy induced by chronic stress. We here report that phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a mediator for chronic stress-induced depression-like behaviors and neuronal atrophy in mice. One-month chronic restraint stress (CRS) up-regulated PTEN signaling pathway in the PFC of mice as indicated by increasing levels of PTEN, p-MEK, and p-ERK but decreasing levels of p-AKT. Over-expression of Pten in the PFC led to an increase of depression-like behaviors, whereas genetic inactivation or knockdown of Pten in the PFC prevented the CRS-induced depression-like behaviors. In addition, systemic administration of PTEN inhibitor was also able to prevent these behaviors. Cellular examination showed that Pten over-expression or the CRS treatment resulted in PFC neuron atrophy, and this atrophy was blocked by genetic inactivation of Pten or systemic administration of PTEN inhibitor. Furthermore, possible causal link between Pten and glucocorticoids was examined. In chronic dexamethasone (Dex, a glucocorticoid agonist) treatment-induced depression model, increased PTEN levels were observed, and depression-like behaviors and PFC neuron atrophy were attenuated by the administration of PTEN inhibitor. Our results indicate that PTEN serves as a key mediator in chronic stress-induced neuron atrophy as well as depression-like behaviors, providing molecular evidence supporting the synaptic plasticity theory of depression. |
format | Online Article Text |
id | pubmed-7998021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79980212021-04-16 PTEN in prefrontal cortex is essential in regulating depression-like behaviors in mice Wang, Xiao-Qing Zhang, Lei Xia, Zhong-Yuan Chen, Jia-Yin Fang, Yiru Ding, Yu-Qiang Transl Psychiatry Article Chronic stress is an environmental risk factor for depression and causes neuronal atrophy in the prefrontal cortex (PFC) and other brain regions. It is still unclear about the molecular mechanism underlying the behavioral alterations and neuronal atrophy induced by chronic stress. We here report that phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a mediator for chronic stress-induced depression-like behaviors and neuronal atrophy in mice. One-month chronic restraint stress (CRS) up-regulated PTEN signaling pathway in the PFC of mice as indicated by increasing levels of PTEN, p-MEK, and p-ERK but decreasing levels of p-AKT. Over-expression of Pten in the PFC led to an increase of depression-like behaviors, whereas genetic inactivation or knockdown of Pten in the PFC prevented the CRS-induced depression-like behaviors. In addition, systemic administration of PTEN inhibitor was also able to prevent these behaviors. Cellular examination showed that Pten over-expression or the CRS treatment resulted in PFC neuron atrophy, and this atrophy was blocked by genetic inactivation of Pten or systemic administration of PTEN inhibitor. Furthermore, possible causal link between Pten and glucocorticoids was examined. In chronic dexamethasone (Dex, a glucocorticoid agonist) treatment-induced depression model, increased PTEN levels were observed, and depression-like behaviors and PFC neuron atrophy were attenuated by the administration of PTEN inhibitor. Our results indicate that PTEN serves as a key mediator in chronic stress-induced neuron atrophy as well as depression-like behaviors, providing molecular evidence supporting the synaptic plasticity theory of depression. Nature Publishing Group UK 2021-03-26 /pmc/articles/PMC7998021/ /pubmed/33771972 http://dx.doi.org/10.1038/s41398-021-01312-y Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wang, Xiao-Qing Zhang, Lei Xia, Zhong-Yuan Chen, Jia-Yin Fang, Yiru Ding, Yu-Qiang PTEN in prefrontal cortex is essential in regulating depression-like behaviors in mice |
title | PTEN in prefrontal cortex is essential in regulating depression-like behaviors in mice |
title_full | PTEN in prefrontal cortex is essential in regulating depression-like behaviors in mice |
title_fullStr | PTEN in prefrontal cortex is essential in regulating depression-like behaviors in mice |
title_full_unstemmed | PTEN in prefrontal cortex is essential in regulating depression-like behaviors in mice |
title_short | PTEN in prefrontal cortex is essential in regulating depression-like behaviors in mice |
title_sort | pten in prefrontal cortex is essential in regulating depression-like behaviors in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998021/ https://www.ncbi.nlm.nih.gov/pubmed/33771972 http://dx.doi.org/10.1038/s41398-021-01312-y |
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