MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies
Ye Li, … , Wenjing Wang, Shu Yan Yu
Ye Li, … , Wenjing Wang, Shu Yan Yu
Published July 6, 2021
Citation Information: J Clin Invest. 2021;131(16):e148853. https://doi.org/10.1172/JCI148853.
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MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies

Abstract

Depression is a neuropsychiatric disease associated with neuronal anomalies within specific brain regions. In the present study, we screened microRNA (miRNA) expression profiles in the dentate gyrus (DG) of the hippocampus and found that miR-26a-3p was markedly downregulated in a rat model of depression, whereas upregulation of miR-26a-3p within DG regions rescued the neuronal deterioration and depression-like phenotypes resulting from stress exposure, effects that appear to be mediated by the PTEN pathway. The knockdown of miR-26a-3p in DG regions of normal control rats induced depression-like behaviors, effects that were accompanied by activation of the PTEN/PI3K/Akt signaling pathway and neuronal deterioration via suppression of autophagy, impairments in synaptic plasticity, and promotion of neuronal apoptosis. In conclusion, these results suggest that miR-26a-3p deficits within the hippocampal DG mediated the neuronal anomalies contributing to the display of depression-like behaviors. This miRNA may serve as a potential therapeutic target for the treatment of depression.

Authors

Ye Li, Cuiqin Fan, Liyan Wang, Tian Lan, Rui Gao, Wenjing Wang, Shu Yan Yu

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Figure 3

Knockdown of miR-26a-3p within the DG induced depression-like behaviors in normal rats.

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Knockdown of miR-26a-3p within the DG induced depression-like behaviors ...
(A) Schematic of AAV vectors engineered to knock down miR-26a-3p or a vector control construct. (B) Experimental paradigm for virus injection and behavioral testing. D, day. (C) Illustration of bilateral virus injection site in the DG hippocampus. Scale bar: 20 μm. (D) Quantitative real-time PCR was used to validate the efficiency of miR-26a-3p knockdown. n = 6 rats per group. Three independent biological replicate experiments were performed for each group. (E) Knockdown of miR-26a-3p within the DG decreased sucrose consumption in the sucrose preference test and (F) increased immobility times and decreased swimming times of rats in the forced-swim test. n = 18 rats per group for behavioral test. Knockdown of miR-26a-3p in DG neurons produced changes in (G) mEPSCs, (H) sEPSCs, and (I) spontaneous burst activity. n = 10 cells from 6 rats per group in G and H; n = 16 cells from 6 rats per group in I. Electrophysiological recordings were repeated in at least 3 independent experiments. Data are presented as mean ± SEM. **P < 0.01 vs. WT; #P < 0.05, ##P < 0.01 vs. AAV-control (WT + AAV-control) by 1-way ANOVA with post hoc Tukey’s correction. Ctrl, control.