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j.neulet.2015.03.028.pdf | 544.8 kB | Adobe PDF | 見る/開く |
タイトル: | Inhibition of histone deacetylases enhances the function of serotoninergic neurons in organotypic raphe slice cultures. |
著者: | Asaoka, Nozomi Nagayasu, Kazuki https://orcid.org/0000-0002-7438-732X (unconfirmed) Nishitani, Naoya Yamashiro, Mayumi Shirakawa, Hisashi https://orcid.org/0000-0002-4129-0978 (unconfirmed) Nakagawa, Takayuki https://orcid.org/0000-0003-1890-0843 (unconfirmed) Kaneko, Shuji https://orcid.org/0000-0001-5152-5809 (unconfirmed) |
著者名の別形: | 中川, 貴之 |
キーワード: | Histone deacetylase Serotonin Raphe slice cultures Trichostatin A AMPA receptor Ca(2+)/calmodulin-dependent kinase II |
発行日: | 23-Apr-2015 |
出版者: | Elsevier |
誌名: | Neuroscience letters |
巻: | 593 |
開始ページ: | 72 |
終了ページ: | 77 |
抄録: | Inhibition of histone deacetylases (HDACs) is a promising approach for the treatment of mood disorders. However, the effects of HDAC inhibition on the serotonin (5-HT) system, a common target for psychiatric disorders, are poorly understood. Here, we show that a broad-spectrum HDAC inhibitor, trichostatin A (TSA), enhances the function of 5-HT neurons in organotypic raphe slice cultures. Sustained treatment with TSA (1μM) for 2 or 4 days significantly increased the 5-HT tissue content and tryptophan hydroxylase 2 (TPH2) expression, which were accompanied by hyper-acetylation of histone H3 in the promoter region of the TPH2 gene. TSA treatment for 4 days increased the extracellular 5-HT level, which was significantly suppressed in the presence of the selective AMPA receptor (AMPAR) antagonist NBQX. Moreover, the expression of both the AMPAR subunit GluA2 and Ca(2+)/calmodulin-dependent kinase II α (CaMKIIα) mRNAs were significantly increased by TSA treatment. Co-treatment with the CaMKII inhibitors KN-62 and KN-93 prevented the TSA-induced increase in 5-HT release, but had no effect on the increases in 5-HT tissue content. These results suggest that inhibition of HDACs increases 5-HT synthesis and release by epigenetic mechanisms, and that 5-HT release is mediated by the enhancement of AMPAR-mediated excitatory inputs and CaMKII signaling. |
著作権等: | © 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ The full-text file will be made open to the public on 23 April 2016 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 This is not the published version. Please cite only the published version. |
URI: | http://hdl.handle.net/2433/200191 |
DOI(出版社版): | 10.1016/j.neulet.2015.03.028 |
PubMed ID: | 25796177 |
出現コレクション: | 学術雑誌掲載論文等 |
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