miR-96 Inhibits SV2C to Promote Depression-Like Behavior and Memory Disorders in Mice

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.

Sesamol ameliorates dextran sulfate sodium-induced depression-like and anxiety-like behaviors in colitis mice: the potential involvement of the gut–brain axis

“…GSH is an important antioxidant, which markedly decreases depression-like behavior in mice intraperitoneally injected with LPS. 57 Furthermore, sesomol supplementation along with intraperitoneal injections of D-galactose also modifies the effects of oxidative stress caused by the Nrf2/ARE antioxidant defense system. 17 In the current work, sesamol alleviated the Nrf2 antioxidant signaling pathway in the brain of DSS-induced colitis mice, which, to the best of our knowledge, has not been found before.…”

A New Player in Depression: MiRNAs as Modulators of Altered Synaptic Plasticity

“…Cell experiments also confirmed that miR-133a and miR-128 targeted Sv2A 3 UTR to inhibit its expression [60]. Another study on the LPS-induced model showed that miR-96 was targeted and negatively regulated SV2C expression in the hippocampal CA1 region, decreased 5-hydroxyindole acetic acid (5-HT) and dopamine (DA) release, and induced the development of depres-sion [61]. MiR-34a-5p expression increased in the hippocampus of mice exposed to chronic stress.…”

Clinical Insights into MicroRNAs in Depression: Bridging Molecular Discoveries and Therapeutic Potential

“…Intriguingly, the use of an anti-miR to miR-144-3p, administered subcutaneously, has led to a marked reduction in depression-related phenotypes in stress-prone mice [ 152 ]. Similarly, the increased expression of miR-96 has led to a decrease in the synaptic vesicle glycoprotein 2 family protein which is associated with depression-like behavior, while inhibiting miR-96 using anti-miR decreased depression-like behavior and memory impairment in mice [ 153 ].…”