Valproate recovers the inhibitory effect of dexamethasone on the proliferation of the adult dentate gyrus-derived neural precursor cells via GSK-3 beta and beta-catenin pathway

Boku, Shuken; Nakagawa, Shin; Masuda, Takahiro; Nishikawa, Hiroyuki; Kato, Akiko; Takamura, Naoki; Omiya, Yuki; Kitaichi, Yuji; Inoue, Takeshi; Kusumi, Ichiro

Valproate recovers the inhibitory effect of dexamethasone on the proliferation of the adult dentate gyrus-derived neural precursor cells via GSK-3 beta and beta-catenin pathway

Boku, Shuken; Nakagawa, Shin; Masuda, Takahiro et al.

European journal of pharmacology, 2014, 723, 425-430

Permalink : https://hdl.handle.net/2115/56639

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アクセス権	open access
URI	https://hdl.handle.net/2115/56639
タイトル	Valproate recovers the inhibitory effect of dexamethasone on the proliferation of the adult dentate gyrus-derived neural precursor cells via GSK-3 beta and beta-catenin pathway
著者	Boku, Shuken ; Nakagawa, Shin ; Masuda, Takahiro ; Nishikawa, Hiroyuki ; Kato, Akiko ; Takamura, Naoki ; Omiya, Yuki ; Kitaichi, Yuji ; Inoue, Takeshi ; Kusumi, Ichiro
e-Rad_Researcher 60455665 著者名 Boku, Shuken
e-Rad_Researcher 60360905 著者名 Nakagawa, Shin
著者名 Masuda, Takahiro
著者名 Nishikawa, Hiroyuki
著者名 Kato, Akiko
著者名 Takamura, Naoki
著者名 Omiya, Yuki
著者名 Kitaichi, Yuji
e-Rad_Researcher 70250438 著者名 Inoue, Takeshi
e-Rad_Researcher 30250426 著者名 Kusumi, Ichiro
言語	英語
キーワード	Neurogenesis
	Glucocorticoid
	Mood disorder
	Mood stabilizer
	Hippocampus
発行日	2014-01-15
出版者	Elsevier science bv
収録物名	European journal of pharmacology
巻(号)	723
ページ	425-430
抄録	Neurogenesis in the adult dentate gyrus (DC) is decreased in rodent models for mood disorders. Mood stabilizers including lithium (Li) and valproate (VPA) increase it. These increasing effects of Li and VPA on neurogenesis in adult DG are considered to be one of the therapeutic actions of Li and VPA, but their molecular mechanism remains unclear. We have already reported that Li recovers the inhibitory effects of dexamethasone (DEX), an agonist of glucocorticoid receptor, on the proliferation of adult rat DG-derived neural precursor cells (ADP) via GSK-3 beta and beta-catenin pathway. Following it, here we investigated the mechanism underlying the recovery effects of VPA on DEX-induced decrease of ADP proliferation. VPA is an inhibitor of histone deacetylase (HDAC). However, Trichostatin A, a HDAC inhibitor, had no effect on ADP proliferation. In contrast, SB415286, a specific GSK-3 beta inhibitor, recovered DEX-induced decrease of ADP proliferation. In addition, quercetin (Que), a beta-catenin pathway inhibitor, abolished such a recovery effect of VPA. Moreover, nuclear p-catenin and the expression of cyclin D1 were altered by DEX. VPA and Que like the proliferation. Moreover, VPA increased the phosphorylation of Ser(9), which is known as the inhibitory phosphorylation site of GSK-3 beta. These suggest that HDAC is not involved in the recovery effect of VPA on ADP proliferation and that VPA recovers the inhibitory effects of DEX via increasing the phosphorylation of Ser9 on GsK-3 beta and following up-regulation of beta-catenin pathway. Therefore, GSK-3 beta and beta-catenin pathway might play a role in the increasing effects of VPA on neurogenesis on adult DC. (C) 2013 Elsevier B.V. All rights reserved,
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	0014-2999
NCID	AA00639687
関連情報	PMID 24211784
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.ejphar.2013.10.060