PMID- 28990703 OWN - NLM STAT- MEDLINE DCOM- 20180913 LR - 20211204 IS - 1440-1819 (Electronic) IS - 1323-1316 (Linking) VI - 72 IP - 4 DP - 2018 Apr TI - Effects of maternal separation and antidepressant drug on epigenetic regulation of the brain-derived neurotrophic factor exon I promoter in the adult rat hippocampus. PG - 255-265 LID - 10.1111/pcn.12609 [doi] AB - AIM: Early life stress can induce epigenetic changes through genetic and environmental interactions and is a risk factor for depression. Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression and antidepressant drug action. We investigated epigenetic changes at the BDNF exon I promoter in the hippocampus of adult rats subjected to maternal separation (MS) during early life and treated with an antidepressant drug as adults. METHODS: Rat pups were subjected to MS from postnatal day 1 to 21 and received chronic escitalopram (ESC) as adults. We assessed the effects of MS and ESC on BDNF exon I and DNA methyltransferases (DNMT) mRNA levels (quantitative reverse-transcription polymerase chain reaction), acetylated histone H3, and MeCP2 binding to the BDNF promoter I (chromatin immunoprecipitation followed by real-time polymerase chain reaction), and BDNF protein levels (enzyme-linked immunosorbent assay). RESULTS: The levels of BDNF protein, exon I mRNA, histone H3 acetylation, and DNMT1 and DNMT3a mRNA were altered in the MS group compared with the control group. Significant decreases were observed in the BDNF protein, exon I mRNA, and histone H3 acetylation levels and there were significant increases in DNMT1 and DNMT3a mRNA levels. The comparison between the MS + ESC and MS groups revealed significant increases in BDNF protein, exon I mRNA, and histone H3 acetylation levels and significant decreases in MeCP2 and DNMT1 and DNMT3a mRNA levels. CONCLUSION: These findings indicate that MS induced epigenetic changes at the BDNF exon I promoter and these changes were prevented by antidepressant drug treatment during adulthood. CI - (c) 2017 The Authors. Psychiatry and Clinical Neurosciences (c) 2017 Japanese Society of Psychiatry and Neurology. FAU - Park, Sung Woo AU - Park SW AUID- ORCID: 0000-0001-8601-9084 AD - Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea. AD - Departments of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea. AD - Department of Convergence Biomedical Science, College of Medicine, Inje University, Busan, Republic of Korea. FAU - Seo, Mi Kyoung AU - Seo MK AUID- ORCID: 0000-0002-3368-4950 AD - Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea. FAU - Lee, Jung Goo AU - Lee JG AUID- ORCID: 0000-0003-3393-2667 AD - Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea. AD - Departments of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea. AD - Department of Psychiatry, College of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea. FAU - Hien, Le Thi AU - Hien LT AUID- ORCID: 0000-0002-7638-4798 AD - Departments of Health Science and Technology, Graduate School, Inje University, Busan, Republic of Korea. FAU - Kim, Young Hoon AU - Kim YH AUID- ORCID: 0000-0002-2003-7877 AD - Department of Psychiatry, Gongju National Hospital, Gongju, Republic of Korea. LA - eng PT - Journal Article DEP - 20171114 PL - Australia TA - Psychiatry Clin Neurosci JT - Psychiatry and clinical neurosciences JID - 9513551 RN - 0 (Antidepressive Agents, Second-Generation) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Histones) RN - 0 (Mecp2 protein, rat) RN - 0 (Methyl-CpG-Binding Protein 2) RN - 0 (RNA, Messenger) RN - 0DHU5B8D6V (Citalopram) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases) RN - EC 2.1.1.37 (DNA Methyltransferase 3A) RN - EC 2.1.1.37 (Dnmt1 protein, rat) SB - IM MH - Acetylation MH - Animals MH - Antidepressive Agents, Second-Generation/*pharmacology MH - Brain-Derived Neurotrophic Factor/drug effects/*metabolism MH - Citalopram/*pharmacology MH - DNA (Cytosine-5-)-Methyltransferase 1/drug effects/*metabolism MH - DNA (Cytosine-5-)-Methyltransferases/drug effects/*metabolism MH - DNA Methyltransferase 3A MH - Epigenesis, Genetic/drug effects/*physiology MH - Exons MH - Female MH - Hippocampus/drug effects/*metabolism MH - Histones/drug effects/*metabolism MH - Male MH - *Maternal Deprivation MH - Methyl-CpG-Binding Protein 2/drug effects/*metabolism MH - Pregnancy MH - Promoter Regions, Genetic MH - RNA, Messenger/drug effects/*metabolism MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - BDNF exon I OT - antidepressant drug OT - epigenetic regulation OT - hippocampus OT - maternal separation EDAT- 2017/10/11 06:00 MHDA- 2018/09/14 06:00 CRDT- 2017/10/10 06:00 PHST- 2017/07/14 00:00 [received] PHST- 2017/09/25 00:00 [revised] PHST- 2017/10/03 00:00 [accepted] PHST- 2017/10/11 06:00 [pubmed] PHST- 2018/09/14 06:00 [medline] PHST- 2017/10/10 06:00 [entrez] AID - 10.1111/pcn.12609 [doi] PST - ppublish SO - Psychiatry Clin Neurosci. 2018 Apr;72(4):255-265. doi: 10.1111/pcn.12609. Epub 2017 Nov 14.