Up‐regulated miR‐192‐5p expression rescues cognitive impairment and restores neural function in mice with depression via the Fbln2‐mediated TGF‐β1 signaling pathway. Issue 1 (17th August 2018)

• Record Type: Journal Article
• Authors: Tang, Chao-Zhi; Yang, Jun‐Tang; Liu, Qing-Hui; Wang, Ya-Ru; Wang, Wen-Sheng
• Is Part Of: FASEB journal. Volume 33:Issue 1(2019)
• Page Start: 606
• Page End: 618
• Publication Date: 2018-08-17
• Subjects: synaptic transmission -- hippocampal dentate gyrus -- dendrite -- cAMP -- HPLC mass spectrometry; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201800210RR
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: Depression represents a condition characterized by cognitive deficits and neural dysfunction and has recently been correlated with microRNAs (miRs) and their respective target genes. The present study was conducted with the goal of investigating the expression of miR‐192‐5p and its target gene fibulin (Fbln)‐2 in an attempt to evaluate their roles in the occurrence and progression of cognitive impairment and neural function in mice with chronic unpredictable mild stress (CUMS)–induced depression through regulation of the TGF‐β1 signal transduction pathway. Verification of the targeting relationship between miR‐192‐5p and Fbln2 was provided in the form of initial bioinformatics prediction, followed by a further verification in the form of a dual‐luciferase reporter gene assay. Normal mice and models induced by CUMS were assigned into various groups, whereas mimics, inhibitors, and small interfering RNA were introduced to validate the regulatory mechanism by which miR‐192‐5p regulates Fbln2 depression. Novel object recognition, tail suspension testing, and Morris water maze were all employed 28 d after transfection. Hippocampal electrophysiological recordings, Golgi staining, HPLC mass spectrometry, and fluorescence immunohistochemistry were performed to further evaluate cognitive function and neuron regeneration. CUMS‐induced depression was determined to represent a predisposing factor for cognitive impairment and damage to neural function in mice, highlighted by novel object recognition, learning and memory abilities, population spike amplitude, synaptic transmission, cAMP levels, neuronal regeneration, and increased behavioral changes that resemble depression. Furthermore, increased Fbln2 expression, an activated TGF‐βl signaling pathway, and decreased expression of miR‐192‐5p, synaptophysin, brain‐derived neurotrophic factor, N ‐methyl‐d ‐aspartate receptor subunit 2B, and calmodulin‐dependent protein kinase II were noted. Up‐regulated miR‐192‐5p targeting Fbln2 acts to alleviate CUMS‐induced depression by inhibiting the TGF‐β1 signaling pathway, resulting in the enhanced cognitive function in novel object recognition, learning and memory ability, population spike amplitude, synaptic transmission, neuron regeneration, and alleviation of behavioral symptoms. The central findings of the present study indicate that up‐regulated levels of miR‐192‐5p expression act to suppress activation of the TGF‐β1 signaling pathway by means of binding to Fbln2, thereby ameliorating cognitive impairment and strengthening neural function in a mouse model of depression.—Tang, C.‐Z., Yang, J.‐T., Liu, Q.‐H., Wang, Y.‐R., Wang, W.‐S., Up‐regulated miR‐192‐5p expression rescues cognitive impairment and restores neural function in mice with depression via the Fbln2‐mediated TGF‐β1 signaling pathway. FASEB J. 33, 606–618 (2019). www.fasebj.org