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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Research Article Neuroscience

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 6

Knockdown of miR-26a-3p within the DG of normal rats induced neuronal apoptosis.

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Knockdown of miR-26a-3p within the DG of normal rats induced neuronal ap...
(A) Representative confocal microscopic images showing expression of cleaved caspase-3 and DCX within the DG of different groups. Scale bars: 50 μm. n = 6 rats per group and at least 4–6 images from 1 animal. (B) Knockdown of miR-26a-3p increased protein levels of proapoptotic factors in the DG. n = 6 rats per group. Western blotting results were from the same samples and run in parallel in different gels. Three independent biological replicate experiments were performed. (C) Representative electron micrographs showing nuclear chromatin abnormalities in DG neurons of different groups. Scale bars: 1 μm. n = 6 per group and at least 5 pyramidal neurons from 1 animal. Immunofluorescence and electron microscopy experiments were repeated at least 3 times and quantitation was done for representative samples from each group. Data are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 vs. WT; #P < 0.05, ##P < 0.01, ###P < 0.001 vs. AAV-control (WT + AAV-control) by 1-way ANOVA with Tukey’s post hoc correction. Ctrl, control.