In utero exposure to valproic acid induces neocortical dysgenesis via dysregulation of neural progenitor cell proliferation/differentiation

Kimino Fujimura, Takayuki Mitsuhashi, Shinsuke Shibata, Sachiko Shimozato, Takao Takahashi

研究成果: Article査読

16 被引用数 (Scopus)

抄録

Valproic acid (VPA), a widely used antiepileptic drug, is an inhibitor of histone deacetylases, which epigenetically modify cell prolifera-tion/differentiation in developing tissues. A series of recent clinical studies in humans reported that VPA exposure in utero impaired histogenesis and the development of the central nervous system, leading to increased risks of congenital malformation and the impairment of higher brain functions in children. In the present study conducted in mice, we report that VPA exposure in utero (1) increases the amount of acetylated histone proteins, (2) alters the expression of G1-phase regulatory proteins, (3) inhibits the cell cycle exit of neural progenitor cells during the early stage of neocortical histogenesis, and (4) increases the production of projection neurons distributed in the superficial neocortical layers in embryonic brains. Together, our findings show that VPA exposure in utero alters proliferation/differentiation characteristics of neural progenitor cells and hence leads to the neocortical dysgenesis.

本文言語English
ページ(範囲)10908-10919
ページ数12
ジャーナルJournal of Neuroscience
36
42
DOI
出版ステータスPublished - 2016 10 19

ASJC Scopus subject areas

  • 神経科学(全般)

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