title: Impaired GABA synthesis, uptake and release are associated with depression-like behaviors induced by chronic mild stress.
abstract: 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.
authors.affiliation: Department of Pharmacology, Qingdao University, School of Pharmacy, Qingdao, China.
authors.forename: K
authors.initials: K
authors.lastname: Ma
authors.affiliation: State Key Lab of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|Department of Biology, College of Life Science, University of Science and Technology of China, Hefei, China.
authors.forename: A
authors.initials: A
authors.lastname: Xu
authors.affiliation: State Key Lab of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: S
authors.initials: S
authors.lastname: Cui
authors.affiliation: State Key Lab of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: M-R
authors.initials: MR
authors.lastname: Sun
authors.affiliation: State Key Lab of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Xue
authors.affiliation: Department of Pharmacology, Qingdao University, School of Pharmacy, Qingdao, China.|State Key Lab of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|Department of Biology, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: J-H
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D003865:Major Depressive Disorder / Q000503:physiopathology* / Q000523:psychology*; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000473:pathology; D017397:Prefrontal Cortex / Q000503:physiopathology*; D013315:Stress, Psychological / Q000150:complications* / Q000503:physiopathology* / Q000523:psychology; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid