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. 2016 Oct 4;6(10):e910. doi: 10.1038/tp.2016.181

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Copyright © 2016 The Author(s)

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/

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miRNAs are short (20~23 nucleotides) endogenous single-stranded RNAs that can regulate messenger RNA (mRNA) expression. The mature miRNAs and Argonaute (Ago) proteins form the RNA-induced silencing complex (RISC), a ribonucleoprotein complex that mediated post-transcriptional mRNA silencing. The complementary base pairing of miRNAs guides RISC to target their mRNAs, which are degraded, destabilized or translationally inhibited by the Ago protein. Chronic environment stress triggers a series of miRNA alteration in the medial prefrontal cortices. Subsequently, the upregulated miR-15b-5p, miRNA-879-5p, miRNA-582-5p and miRNA-144-3p directly downregulate their targeted mRNAs that encode GABA transporter (GAT)-3, vesicular GAT (VGAT) and GAD-67 proteins. Finally, these changes lead to the deterioration of GABA uptake and release in the presynaptic terminals of GABAergic neurons, which lead to the pathogenesis of major depression. GAD, glutamate decarboxylase.