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Impaired GABA synthesis, uptake and release are associated with depression-like behaviors induced by chronic mild stress
Major depression is a prevalent emotion disorder. Chronic stressful life in genetically susceptible individuals is presumably a major etiology that leads to neuron and synapse atrophy in the limbic system. Molecular mechanisms underlying the pathological changes remain elusive. Mice were treated by...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5315548/ https://www.ncbi.nlm.nih.gov/pubmed/27701406 http://dx.doi.org/10.1038/tp.2016.181 |
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author | Ma, K Xu, A Cui, S Sun, M-R Xue, Y-C Wang, J-H |
author_facet | Ma, K Xu, A Cui, S Sun, M-R Xue, Y-C Wang, J-H |
author_sort | Ma, K |
collection | PubMed |
description | Major depression is a prevalent emotion disorder. Chronic stressful life in genetically susceptible individuals is presumably a major etiology that leads to neuron and synapse atrophy in the limbic system. Molecular mechanisms underlying the pathological changes remain elusive. Mice were treated by chronic unpredictable mild stress (CUMS) until they demonstrated depression-like behavior. GABA release in the medial prefrontal cortex was evaluated by cell electrophysiology and imaging. Molecular profiles related to GABA synthesis and uptake were investigated by the high-throughput sequencings of microRNAs and mRNAs as well as western blot analysis in this cortical area. In CUMS-induced depression mice, there appear the decreases in the innervation and function of GABAergic axons and in the levels of mRNAs and proteins of glutamate decarboxylase-67, vesicular GABA transporter and GABA transporter-3. miRNA-15b-5p, miRNA-144-3p, miRNA-582-5p and miRNA-879-5p that directly downregulate such mRNAs increase in this cortex. Our results suggest that chronic mild stress impairs GABA release and uptake by upregulating miRNAs and downregulating mRNAs and proteins, which may constitute the subcellular and molecular mechanisms for the lowered GABA tone in major depression. |
format | Online Article Text |
id | pubmed-5315548 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53155482017-02-27 Impaired GABA synthesis, uptake and release are associated with depression-like behaviors induced by chronic mild stress Ma, K Xu, A Cui, S Sun, M-R Xue, Y-C Wang, J-H Transl Psychiatry Original Article Major depression is a prevalent emotion disorder. Chronic stressful life in genetically susceptible individuals is presumably a major etiology that leads to neuron and synapse atrophy in the limbic system. Molecular mechanisms underlying the pathological changes remain elusive. Mice were treated by chronic unpredictable mild stress (CUMS) until they demonstrated depression-like behavior. GABA release in the medial prefrontal cortex was evaluated by cell electrophysiology and imaging. Molecular profiles related to GABA synthesis and uptake were investigated by the high-throughput sequencings of microRNAs and mRNAs as well as western blot analysis in this cortical area. In CUMS-induced depression mice, there appear the decreases in the innervation and function of GABAergic axons and in the levels of mRNAs and proteins of glutamate decarboxylase-67, vesicular GABA transporter and GABA transporter-3. miRNA-15b-5p, miRNA-144-3p, miRNA-582-5p and miRNA-879-5p that directly downregulate such mRNAs increase in this cortex. Our results suggest that chronic mild stress impairs GABA release and uptake by upregulating miRNAs and downregulating mRNAs and proteins, which may constitute the subcellular and molecular mechanisms for the lowered GABA tone in major depression. Nature Publishing Group 2016-10 2016-10-04 /pmc/articles/PMC5315548/ /pubmed/27701406 http://dx.doi.org/10.1038/tp.2016.181 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Ma, K Xu, A Cui, S Sun, M-R Xue, Y-C Wang, J-H Impaired GABA synthesis, uptake and release are associated with depression-like behaviors induced by chronic mild stress |
title | Impaired GABA synthesis, uptake and release are associated with depression-like behaviors induced by chronic mild stress |
title_full | Impaired GABA synthesis, uptake and release are associated with depression-like behaviors induced by chronic mild stress |
title_fullStr | Impaired GABA synthesis, uptake and release are associated with depression-like behaviors induced by chronic mild stress |
title_full_unstemmed | Impaired GABA synthesis, uptake and release are associated with depression-like behaviors induced by chronic mild stress |
title_short | Impaired GABA synthesis, uptake and release are associated with depression-like behaviors induced by chronic mild stress |
title_sort | impaired gaba synthesis, uptake and release are associated with depression-like behaviors induced by chronic mild stress |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5315548/ https://www.ncbi.nlm.nih.gov/pubmed/27701406 http://dx.doi.org/10.1038/tp.2016.181 |
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