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Tricyclic Antidepressant Amitriptyline Indirectly Increases the Proliferation of Adult Dentate Gyrus-Derived Neural Precursors: An Involvement of Astrocytes

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この文献へのリンクには次のURLを使用してください:http://hdl.handle.net/2115/54114

タイトル: Tricyclic Antidepressant Amitriptyline Indirectly Increases the Proliferation of Adult Dentate Gyrus-Derived Neural Precursors: An Involvement of Astrocytes
著者: Boku, Shuken 著作を一覧する
Hisaoka-Nakashima, Kazue 著作を一覧する
Nakagawa, Shin 著作を一覧する
Kato, Akiko 著作を一覧する
Kajitani, Naoto 著作を一覧する
Inoue, Takeshi 著作を一覧する
Kusumi, Ichiro 著作を一覧する
Takebayashi, Minoru 著作を一覧する
発行日: 2013年11月18日
出版者: Public library science
誌名: Plos one
巻: 8
号: 11
開始ページ: e79371
出版社 DOI: 10.1371/journal.pone.0079371
抄録: Antidepressants increase the proliferation of neural precursors in adult dentate gyrus (DG), which is considered to be involved in the therapeutic action of antidepressants. However, the mechanism underlying it remains unclear. By using cultured adult rat DG-derived neural precursors (ADP), we have already shown that antidepressants have no direct effects on ADP. Therefore, antidepressants may increase the proliferation of neural precursors in adult DG via unknown indirect mechanism. We have also shown that amitriptyline (AMI), a tricyclic antidepressant, induces the expressions of GDNF, BDNF, FGF2 and VEGF, common neurogenic factors, in primary cultured astrocytes (PCA). These suggest that AMI-induced factors in astrocytes may increase the proliferation of neural precursors in adult DG. To test this hypothesis, we examined the effects of AMI-induced factors and conditioned medium (CM) from PCA treated with AMI on ADP proliferation. The effects of CM and factors on ADP proliferation were examined with BrdU immunocytochemistry. AMI had no effect on ADP proliferation, but AMI-treated CM increased it. The receptors of GDNF, BDNF and FGF2, but not VEGF, were expressed in ADP. FGF2 significantly increased ADP proliferation, but not BDNF and GDNF. In addition, both of a specific inhibitor of FGF receptors and anti-FGF2 antibody significantly counteracted the increasing effect of CM on ADP proliferation. In addition, FGF2 in brain is mainly derived from astrocytes that are key components of the neurogenic niches in adult DG. These suggest that AMI may increase ADP proliferation indirectly via PCA and that FGF2 may a potential candidate to mediate such an indirect effect of AMI on ADP proliferation via astrocytes.
資料タイプ: article
URI: http://hdl.handle.net/2115/54114
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 中川 伸

 

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