OBJECTIVES: 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. CONCLUSION: 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.
OBJECTIVES: 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. CONCLUSION: 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: James Johnson; Edward Alain B Pajarillo; Equar Taka; Romonia Reams; Deok-Soo Son; Michael Aschner; Eunsook Lee Journal: Neurotoxicology Date: 2017-06-10 Impact factor: 4.294
Authors: Gabriel Oh; Sun-Chong Wang; Mrinal Pal; Zheng Fei Chen; Tarang Khare; Mamoru Tochigi; Catherine Ng; Yeqing A Yang; Andrew Kwan; Zachary A Kaminsky; Jonathan Mill; Cerisse Gunasinghe; Jennifer L Tackett; Irving I Gottesman; Gonneke Willemsen; Eco J C de Geus; Jacqueline M Vink; P Eline Slagboom; Naomi R Wray; Andrew C Heath; Grant W Montgomery; Gustavo Turecki; Nicholas G Martin; Dorret I Boomsma; Peter McGuffin; Rafal Kustra; Art Petronis Journal: Biol Psychiatry Date: 2014-07-01 Impact factor: 13.382
Authors: Robyn M Brown; Eva Guerrero-Hreins; Wendy A Brown; Carel W le Roux; Priya Sumithran Journal: Nat Rev Endocrinol Date: 2021-07-14 Impact factor: 43.330