Direct evidence for epigenetic changes that occur during brain development and underlie sensitivity to stress comes from work by Meaney and colleagues65. Some rat mothers naturally display high levels of nurturing behaviours, such as licking, grooming and arched-back nursing, whereas others display low levels of such behaviours. Offspring of high-nurturing mothers are less anxious and display more nurturing maternal behaviour towards their own pups. They also have attenuated corticosterone responses to stress and express higher levels of GR in the hippocampus. This enhanced GR expression is mediated in part by the transcription factor nerve growth factor-inducible protein A (NGFI-A; also known as EGR1) (FIG. 1). Interestingly, pups that received little nurturing show increased methylation of the GR gene promoter at the NGFI-A binding site in the hippocampus, an epigenetic change that is associated with reduced GR expression66. This difference in methylation emerges in the first week of life and persists into adulthood. As a result, adult offspring of low-nurturing mothers have reduced hippocampal GR expression, which contributes to the behavioural deficits that these animals exhibit and pass on to their
