Epigenetic programming by maternal behavior and pharmacological intervention. Nature versus nurture: let's call the whole thing off.

The nature of maternal care that an infant receives can effect the child's emotional and cognitive development, which is endured into adulthood. Similarly, maternal behavior in rodents is associated with long-term programming of individual differences in behavioral and hypothalamic-pituitary-adrenal responses to stress in the offspring. One critical question is how is such 'environmental programming' established and sustained in the offspring? This review discusses a novel mechanism to explain how maternal licking/grooming behavior in the rat can alter the hippocampal glucocorticoid receptor (GR) expression in the offspring, which concomitantly alters the HPA axis and the stress responsiveness of these animals. Both in vivo and in vitro studies show that maternal behavior increases GR expression in the offspring via increased hippocampal serotonergic tone accompanied by increased histone acetylase transferase activity, histone acetylation and DNA demethylation mediated by the transcription factor NGFI-A. In summary, this research demonstrates that an epigenetic state of a gene can be established through early-in-life experience, and is potentially reversible in adulthood. Accordingly, epigenetic modifications of specific genomic regions in response to variations in environmental conditions might serve as a major source of variation in biological and behavioral phenotypes.