The psychopathology of prenatal stress: The role of epigenetic regulation of brain-derived neurotrophic factor (BDNF) promoter

Prenatal stress (PS) has been shown to influence the development of the foetal brain and to increase the risk of developing psychiatric disorders in adulthood. The exact mechanisms underlying the relation between PS and adult psychopathology are poorly understood though. Recently, it has been suggested that epigenetic regulation, involving e.g. changes in DNA methylation, may play an essential role in establishing long-lasting changes in brain function and behaviour associated with developmental stress exposure. In the present study, we examined the effects of PS on methylation levels of brain-derived neurotrophic factor (BDNF) promoter (I, IV, and IX) within the hippocampus and frontal cortex in a maternal restraint stress paradigm of PS in C57BL6 mice. In addition, the same mice had been used for behavioural studies on cognition, anxiety and depression before. Particularly female offspring exposed to PS showed different methylation of distinct CpG sites within the promoter region of BDNF in both the hippocampus and frontal cortex compared to control mice. Also gender-specific changes of methylation patterns in unstressed and stressed animals have been revealed in promoter IV and IX. Further, PS induced different behaviour of female and male mice in the object recognition task and sucrose consumption test. Studying the role of epigenetics in the light of developmental stress exposure may unravel new biochemical pathways in the aetiology of psychiatric disorders.