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.
Highlights
Depressive disorders have exhibited a progressive increase among younger age demographics and are often a detrimental contributor to serious impairments from both personal and social functioning points of view (Zhou et al, 2017)
enzyme-linked immunosorbent assay (ELISA) (Figure 1F) results indicated that compared with the sham-operated mice, the TNFα and IL-1β levels in the brain CA1 region were elevated in LPS-treated mice
The findings mentioned earlier demonstrated that LPS induced depression-like behavior and memory disorders in mice, and miR-96 was upregulated in the CA1 region of the brain in LPS-treated mice
Summary
Depressive disorders have exhibited a progressive increase among younger age demographics and are often a detrimental contributor to serious impairments from both personal and social functioning points of view (Zhou et al, 2017). Neonatal immune activation has been linked with depressionlike behaviors in adult mice, whereas major depressive disorder has been reported to be a risk factor in memory impairment, illustrated by poor memory for positive reinforcing stimuli (Doosti et al, 2013; Sorenson et al, 2014). MiR-96 may regulate insulin-like growth factor 1 receptor expression to influence the effects of sevoflurane on learning and memory impairment in rats (Xu et al, 2019). Previous studies have suggested that the serotonin 5-hydroxytryptamine receptor 1B receptor in the brain is related to aggressive behavior, representing a crucial endophenotype associated with suicidal behavior and a notable element involved in regulating suicidal behavior in depression. We asserted that miR-96 could be used as a potential biomarker of depressive behavior
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