CircSYNDIG1 ameliorates stress-induced abnormal behaviors by suppressing miR-344-5p in mice

Circular RNA (circRNA) plays an important role in diverse stress-related neuropsychiatric disorders like depression, anxiety and cognitive disorders. Here, using a circRNA microarray, we found that circSYNDIG1, an unreported circRNA, was significantly downregulated in the hippocampus of chronic unpredictable mild stress (CUMS) mice and further validated this finding in corticosterone (CORT) and lipopolysaccharide (LPS) mice by qRT-PCR, and it was negatively correlated with depressive- and anxiety-like behaviors of these three stressed mice. Furthermore, the interaction of miR-344-5p and circSYNDIG1 was confirmed by in situ hybridization (FISH) assay in hippocampus and dual luciferase reporter assay in 293 T cells. And miR-344-5p mimics could simulate the dendritic spine density reduction, depressive- and anxiety-like behaviors and memory impairment induced by CUMS. Overexpression of circSYNDIG1 in hippocampus significantly ameliorated these abnormal changes induced by CUMS or miR-344-5p. It indicated that circSYNDIG1 functions as an miR-344-5p sponge to inhibit miR-344-5p impact, resulting in the increase of dendritic spine density and the subsequent amelioration of the abnormal behaviors. Therefore, the downregulation of circSYNDIG1 in hippocampus participates in CUMS-induced depressive and anxiety-like behavior of mice though miR-344-5p. These findings represent the first evidence for the involvement of circSYNDIG1 and its coupling mechanism in depression and anxiety, suggesting that circSYNDIG1 and miR-344-5p might be new targets for the treatment of stress-related disorder.