Open AccessImpaired GABA synthesis, uptake and release are associated with depression-like behaviors induced by chronic mild stress
Author(s) -
Kewei Ma,
Aidong Xu,
Sheng Cui,
Sun Mr,
Xue Yc,
Wang Jh
Publication year - 2016
Publication title -
translational psychiatry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.652
H-Index - 82
ISSN - 2158-3188
DOI - 10.1038/tp.2016.181
Subject(s) - gabaergic , glutamate decarboxylase , prefrontal cortex , neuroscience , glutamate receptor , microrna , chronic stress , synapse , biology , endocrinology , medicine , microbiology and biotechnology , inhibitory postsynaptic potential , biochemistry , receptor , gene , cognition , enzyme
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.