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

Jee Young Seo; Hye-Ryeong Jo; Seung Hoon Lee; Do Gyeong Kim; Huiju Lee; Ye Lim Kim; Young In Choi; Sung Jun Jung; Hyeon Son

doi:10.1016/j.isci.2023.108617

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

iScience. 2023 Dec 2;27(1):108617. doi: 10.1016/j.isci.2023.108617. eCollection 2024 Jan 19.

Authors

Jee Young Seo¹, Hye-Ryeong Jo², Seung Hoon Lee², Do Gyeong Kim¹, Huiju Lee¹, Ye Lim Kim¹, Young In Choi³, Sung Jun Jung^{1

3}, Hyeon Son^{1

4}

Affiliations

¹ Graduate School of Biomedical Science and Engineering, Hanyang Biomedical Research Institute, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea.
² Hanyang University Hospital for Rheumatic Diseases, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea.
³ Department of Physiology, College of Medicine, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea.
⁴ Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, Korea.

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.

Keywords: Behavioral neuroscience; Molecular neuroscience; Neuroscience; Rodent behavior.