TRPC4 deletion elicits behavioral defects in sociability by dysregulating expression of microRNA-138-2.

ABSTRACT: To investigate whether the defects in transient receptor potential canonical 4 (TRPC4), which is strongly expressed in the hippocampus, are implicated in ASD, we examined the social behaviors of mice in which Trpc4 was deleted (Trpc4^-/-). Trpc4^-/- mice displayed the core symptoms of ASD, namely, social disability and repetitive behaviors. In microarray analysis of the hippocampus, microRNA (miR)-138-2, the precursor of miR-138, was upregulated in Trpc4^-/- mice. We also found that binding of Matrin3 (MATR3), a selective miR-138-2 binding nuclear protein, to miR-138-2 was prominently enhanced, resulting in the downregulation of miR-138 in Trpc4^-/- mice. Some parameters of the social defects and repetitive behaviors in the Trpc4^-/- mice were rescued by increased miR-138 levels following miR-138-2 infusion in the hippocampus. Together, these results suggest that Trpc4 regulates some signaling components that oppose the development of social behavioral deficits through miR-138 and provide a potential therapeutic strategy for ASD.

SUBMITTER: Seo JY 

PROVIDER: S-EPMC10770719 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature