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 mechanism...Continue Reading
References
Mar 24, 2000·Science·Y HayashiR Malinow
Aug 23, 2001·Neuron·N BallasG Mandel
Jan 4, 2003·Science·Diego J WaltherMichael Bader
Feb 21, 2006·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Lee E SchechterSharon Rosenzweig-Lipson
Feb 28, 2006·Nature Neuroscience·Nadia M TsankovaEric J Nestler
Sep 2, 2006·Biological Psychiatry·Frederick A SchroederSchahram Akbarian
May 19, 2007·The European Journal of Neuroscience·S E GartsideS J Judge
Jun 8, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Christopher G VecseyMarcelo A Wood
Jul 7, 2007·The Journal of Biological Chemistry·Paresh D PatelCrystal G Pontrello
Sep 18, 2007·The Biochemical Journal·Nagma KhanMaxwell Sehested
Oct 24, 2007·Neuroscience·G T ShishkinaN N Dygalo
Dec 27, 2008·Neuron·Emiliana BorrelliPaolo Sassone-Corsi
Jan 17, 2009·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Francis Rodriguez BambicoGabriella Gobbi
Jun 26, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mohd W AkhtarLisa M Monteggia
Jul 29, 2009·Neurobiology of Disease·Giuseppe FaracoAlberto Chiarugi
Nov 10, 2009·Nature Neuroscience·Chris MurgatroydDietmar Spengler
Jul 21, 2010·Current Opinion in Psychiatry·Marc SchroederHelge Frieling
Aug 12, 2010·British Journal of Pharmacology·Kazuki NagayasuShuji Kaneko
Oct 5, 2010·Nature Neuroscience·Evan ElliottAlon Chen
Apr 26, 2011·Nature Neuroscience·Anders S KristensenStephen F Traynelis
Mar 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Kyung-Min NohR Suzanne Zukin
Mar 30, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Julie EspallerguesOlivier Berton
Oct 12, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ashley N HutchinsonAnne E West
Feb 9, 2013·Molecular Neurobiology·Ul'yana A BoyarskikhNatalia N Kudryavtseva
Aug 24, 2013·Frontiers in Psychiatry·Florian Joachim Raabe, Dietmar Spengler
Citations
Oct 28, 2016·Brain Research Bulletin·Hiroki Imbe, Akihisa Kimura
Jul 7, 2018·CNS Neuroscience & Therapeutics·Hei-Jen HuangHsiu Mei Hsieh-Li
Nov 30, 2018·Molecular Medicine Reports·Yueling WangWenjuan Ma