Environmental Enrichment Increased Bdnf Transcripts in the Prefrontal Cortex: Implications for an Epigenetically Controlled Mechanism

Abstract

Environmental enrichment (EE) is a condition characterized by its complexity regarding social contact, exposure to novelty, tactile stimuli and voluntary exercise, also is considered as a eustress model. The impact of EE on brain physiology and behavioral outcomes may be at least partly underpinned by mechanisms involving the modulation of the brain-derived neurotrophic factor (BDNF), but the connection between specific Bdnf exon expression and their epigenetic regulation remain poorly understood. This study aimed to dissect the transcriptional and epigenetic regulatory effect of 54-day exposure to EE on BDNF by analysing individual BDNF exons mRNA expression and the DNA methylation profile of a key transcriptional regulator of the Bdnf gene, exon IV, in the prefrontal cortex (PFC) of C57BL/6 male mice (sample size = 33). Bdnf exons II, IV, VI and IX mRNA expression were upregulated and methylation levels at two CpG sites of exon IV were reduced in the PFC of EE mice. As deficit in exon IV expression has also been causally implicated in stress-related psychopathologies, we also assessed anxiety-like behavior and plasma corticosterone levels in these mice to determine any potential correlation. However, no changes were observed in EE mice. The findings may suggest an EE-induced epigenetic control of BDNF exon expression via a mechanism involving exon IV methylation. The findings of this study contribute to the current literature by dissecting the Bdnf gene topology in the PFC where transcriptional and epigenetic regulatory effect of EE takes place.

Keywords: BDNF; anxiety; corticosterone; environmental enrichment; epigenetics; methylation.