AUTHOR=Sun Lidong , Bai Donghao , Lin Maoguang , Eerdenidalai , Zhang Li , Wang Fengzhen , Jin Shangwu TITLE=miR-96 Inhibits SV2C to Promote Depression-Like Behavior and Memory Disorders in Mice JOURNAL=Frontiers in Behavioral Neuroscience VOLUME=14 YEAR=2021 URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2020.575345 DOI=10.3389/fnbeh.2020.575345 ISSN=1662-5153 ABSTRACT=

Accumulating evidence continues to emphasize the role of microRNAs as significant contributors to depression-like behavior and memory disorders. The current study aimed to investigate the mechanism by which miR-96 influences depression-like behavior and memory deficit in mice. A depression-like behavior and memory disorder mouse model was initially established by means of intraperitoneal injection with lipopolysaccharide. Memory deficits in the mice were evaluated using the Novel Object Recognition Test and Morris water maze experiments, whereas the Sucrose Preference Experiment and forced swimming experiments were performed to identify depression-like behavior in mice. The levels of tumor necrosis factor-α, malondialdehyde, superoxide dismutase, glutathione, and the monoamine transmitters 5-hydroxytryptamine and dopamine were subsequently detected in the serum. Reverse transcription-quantitative polymerase chain reaction and Western blot analysis evaluated the expression of miR-96 and SV2C expression in the CA1 hippocampal region of the mice. Finally, the relationship of miR-96 and SV2C was verified by dual-luciferase reporter gene assay. Our data indicated that the expression of miR-96 was increased, whereas that of SV2C was decreased in the CA1 region of mice exhibiting depression-like behavior and memory impairment. When miR-96 was downregulated or SV2C was overexpressed via intra-cerebroventricular injection with a miR-96 antagonist (miR-96 antagomir) or overexpression of SV2C vector, the Novel Object Recognition Test and sucrose preference index were increased, whereas the escape latency, the number of water maze platform crossings, and the immobility time of the mice were decreased. The serum levels of tumor necrosis factor-α, interleukin-1β, and malondialdehyde in the mouse CA1 region of mice were reduced, whereas the levels of superoxide dismutase and glutathione were elevated after the downregulation of miR-96 or overexpression of SV2C. Collectively, our study demonstrates that miR-96 negatively regulates the expression of SV2C, which consequently leads to depression-like behavior and memory impairment in mice. Our findings highlight the potential of miR-96-targeted therapeutics.