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Title: Inhibition of histone deacetylases enhances the function of serotoninergic neurons in organotypic raphe slice cultures.
Authors: Asaoka, Nozomi
Nagayasu, Kazuki  kyouindb  KAKEN_id
Nishitani, Naoya
Yamashiro, Mayumi
Shirakawa, Hisashi  kyouindb  KAKEN_id  orcid (unconfirmed)
Nakagawa, Takayuki  kyouindb  KAKEN_id
Kaneko, Shuji  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: 中川, 貴之
Keywords: Histone deacetylase
Raphe slice cultures
Trichostatin A
AMPA receptor
Ca(2+)/calmodulin-dependent kinase II
Issue Date: 23-Apr-2015
Publisher: Elsevier
Journal title: Neuroscience letters
Volume: 593
Start page: 72
End page: 77
Abstract: 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.
Rights: © 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
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.
DOI(Published Version): 10.1016/j.neulet.2015.03.028
PubMed ID: 25796177
Appears in Collections:Journal Articles

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