Histone lysine crotonylation associated epigenetic mechanism dynamically regulates prenatal stress induced anxiety-related behaviour in adolescent offspring.

Abstract

Introduction: This study designed to examine whether social/ environmental experiences can induce the epigenetic modification, and influence the associated physiology and behaviour. To test this, we have used social stress [prenatal stress (PNS)] model and then housed at environmental enrichment (EE) condition to evaluate the interaction between specific epigenetic modification and its influence on behaviour.

Methods: Pregnant rats were randomly divided into a control group, PNS group, and PNS+EE group. PNS and PNS+EE animals were subjected to social defeat (SD) stress during their gestational day (GD) 16-18. PNS animals and their offspring were always housed in standard laboratory condition, PNS+EE animal was housed in EE cage during GD-10 to the pup's age of postnatal day (PND) 30. Animals were tested for anxiety-like behaviour using Open-Field Test (OFT) and memory was examined by passive avoidance test. Western blotting was used to detect the expression pattern of molecules associated with histone crotonylation.

Result: We observed anxiety-like behaviour, memory deficit in the animals experienced PNS. Further, level of Methyl-CpG Binding Protein 2 (MeCP2), repressor element-1 silencing transcription factor (REST), Sirtuin 1(SIRT1), Chromodomain Y-like (CDYL) and Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit (EZH2) and histone methylation (H3K27me3) was elevated. Where as, the expression of p300, histone crotonylation (H3K18Cr) and neuropeptide VGF were suppressed. Notably, EE restore the normal expression pattern of MeCP2, REST, P300, SIRT1, CYDL, EZH2, H3K27me3, H3K18Cr and VGF.

Conclusion: EE reverse the PNS induced alterations, including suppression of histone crotonylation (H3K18Cr), which possibly involved in the regulation of expression of VGF and behaviour.