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김홍원Hongwon Kim

동국대학교

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Nat. Commun., Published: 11 March 2025; 16, 2435 | https://doi.org/10.1038/s41467-025-57699-5 PTN activity in quiescent neural stem cells mediates Shank3 overexpression-induced manic behavior

Hongwon Kim^1,2, Byounggook Cho¹, Hyung Kyu Kim³, Soi Kang¹, Saemin An¹, Daeyeol Kwon¹, Hee Young Kim³ & Jongpil Kim¹

¹Department of Chemistry, Dongguk University, Pildong-ro 1-gil 30, Jung-gu, Seoul 04620, Republic of Korea.
²Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
³Department of Physiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.

Corresponding author
Correspondence to Jongpil Kim.

Abstract

Mania is a complex psychiatric disease characterized by hyperactivity, elevated mood and reduced anxiety. Despite extensive studies on the mechanism of the manic episodes, the molecular targets that control manic pathogenesis remain largely unclear. Here, through single-cell RNA sequencing (scRNA-seq) analysis, we show aberrant adult neurogenesis due to increased numbers of quiescent neural stem cells (qNSC) in a manic mouse model with Shank3 overexpression. Particularly, we found that the excessive Pleiotrophin (PTN), released by dysregulated qNSCs, is a key factor contributing to the manic-like phenotypes in Shank3-overexpressing mouse models. Pharmacological and molecular inhibition of PTN in qNSCs rescued aberrant neurogenesis and effectively alleviated the manic-like social deficits observed in Shank3-overexpressing mice. Taken together, our findings present an approach for modulating PTN activity in qNSCs, proposing it as a promising therapeutic target for manic development.

논문정보

형식Research article
게재일2025년 03월 (BRIC 등록일 2025-03-12)
연구진국내(교신)+국외 연구진
분야 생명과학 > 신경생물학

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