Effects of maternal separation and antidepressant drug on epigenetic regulation of the brain‐derived neurotrophic factor exon I promoter in the adult rat hippocampus

Psychiatry and Clinical Neurosciences - Tập 72 Số 4 - Trang 255-265 - 2018
Sung Woo Park1,2, Mi Kyoung Seo2, Jung Goo Lee3,1,2, Lê Thị Thu Hiền1, Young Hoon Kim4
1Departments of Health Science and Technology, Graduate School Inje University Busan Republic of Korea
2Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea
3Department of Psychiatry, College of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea
4Department of Psychiatry, Gongju National Hospital, Gongju, Republic of Korea

Tóm tắt

AimEarly 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.MethodsRat 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).ResultsThe 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.ConclusionThese findings indicate that MS induced epigenetic changes at the BDNF exon I promoter and these changes were prevented by antidepressant drug treatment during adulthood.

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Psychiatry and Clinical Neurosciences

Tập 72 Số 4

255-265

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