Valproic acid, a histone deacetylase inhibitor, regulates cell proliferation in the adult zebrafish optic tectum

Miki Dozawa, Hiromitsu Kono, Yuki Sato, Yoko Ito, Hideomi Tanaka, Toshio Ohshima*

*この研究の対応する著者

研究成果: Article査読

22 被引用数 (Scopus)

抄録

Background: Valproic acid (VPA) has been used to treat epilepsy and bipolar disorder. Several reports have demonstrated that VPA functions as a histone deacetylase (HDAC) inhibitor. While VPA is known to cause teratogenic changes in the embryonic zebrafish brain, its effects on neural stem cells (NSCs) in both the embryonic and adult zebrafish are not well understood. Results: In this study, we observed a proliferative effect of VPA on NSCs in the embryonic hindbrain. In contrast, VPA reduced cell proliferation in the adult zebrafish optic tectum. Treatment with HDAC inhibitors showed a similar inhibitory effect on cell proliferation in the adult zebrafish optic tectum, suggesting that VPA reduces cell proliferation through HDAC inhibition. Cell cycle progression was also suppressed in the optic tectum of the adult zebrafish brain because of HDAC inhibition. Recent studies have demonstrated that HDAC inhibits the Notch signaling pathway; hence, adult zebrafish were treated with a Notch inhibitor. This increased the number of proliferating cells in the adult zebrafish optic tectum with down-regulated expression of her4, a target of Notch signaling. Conclusions: These results suggest that VPA inhibits HDAC activity and upregulates Notch signaling to reduce cell proliferation in the optic tectum of adult zebrafish.

本文言語English
ページ(範囲)1401-1415
ページ数15
ジャーナルDevelopmental Dynamics
243
11
DOI
出版ステータスPublished - 2014 11 1

ASJC Scopus subject areas

  • 発生生物学

フィンガープリント

「Valproic acid, a histone deacetylase inhibitor, regulates cell proliferation in the adult zebrafish optic tectum」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル