title: Antidepressant-like effect of sodium butyrate (HDAC inhibitor) and its molecular mechanism of action in the rat hippocampus.
abstract: OBJECTIVE
  Epigenetic mechanisms, such as changes in gene expression resulting from chromatin remodeling through histone acetylation, have been implicated in the pathophysiology of depression. However, the antidepressant-like effect of the histone deacetylase inhibitor sodium butyrate (SB) has been inconclusive. The aim of this study was to examine the antidepressant-like effect of SB and elucidate its molecular mechanisms.
  
  
  METHODS
  We examined the antidepressant-like effect of SB in a forced swim test (FST) and a tail suspension test (TST). Hippocampal gene expression analyses using DNA microarray and real-time PCR were undertaken. Western blotting and ChIP assay were undertaken to examine whether histone acetylation was associated with changes in gene expression by SB.
  
  
  RESULTS
  Repeated administration of SB significantly reduced immobility on the FST and the TST, and significantly altered the levels of mRNA for several genes; e.g., upregulation of transthyretin (Ttr) and downregulation of serotonin 2A receptor (Htr2a). Western blotting and ChIP assay revealed selective increases in histone H4 acetylation at the promoter of the Ttr gene with a significant increase in Ttr immunoreactivity 24 h after the final administration of SB.
  
  
  CONCLUSIONS
  These findings suggest the possibility that alterations in gene expression, including upregulation of Ttr and downregulation of several other genes, including Htr2a, may be involved in antidepressant-like effect of SB.
authors.affiliation: Department of Psychiatry and Neurosciences, Division of Frontier Medical Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yamawaki
authors.forename: Manabu
authors.initials: M
authors.lastname: Fuchikami
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morinobu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Segawa
authors.forename: Tomoya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Shigeto
authors.initials: S
authors.lastname: Yamawaki
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D015536:Down-Regulation; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000187:drug effects* / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011228:Prealbumin / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D017670:Sodium Compounds / Q000494:pharmacology*; D013315:Stress, Psychological / Q000235:genetics; D015854:Up-Regulation
chemical_list: D000928:Antidepressive Agents; D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D011228:Prealbumin; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D017670:Sodium Compounds