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

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    • Subject Terms:
      PHYSIOLOGICAL effects of antidepressants; NEUROTROPHINS; NEUROTROPHIC functions; SEPARATION (Psychology); MENTAL depression
    • Abstract:
      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. [ABSTRACT FROM AUTHOR]
    • Abstract:
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