Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

PTN activity in quiescent neural stem cells mediates Shank3 overexpression-induced manic behavior

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月11日

查看全文
  • Hongwon Kim,
  • Byounggook Cho,
  • Hyung Kyu Kim,
  • Soi Kang,
  • Saemin An,
  • Daeyeol Kwon,
  • Hee Young Kim,
  • Jongpil Kim

摘要

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.