Perinatal programming of neurodevelopment: epigenetic mechanisms and the prenatal shaping of the brain.

Abstract

The recent years have witnessed an exponential growth in the knowledge of epigenetic mechanisms, and piling evidence now links DNA methylation and histone modifications with a wide range of physiological processes from embryonic development to memory formation and behavior. Not surprisingly, deregulation of epigenetic modifications is associated with human diseases as well.An important feature of epigenetics is the ability of transducing environmental input into biological signaling, mainly by modulation of the transcriptome in response to a particular scenario. This characteristic generates developmental plasticity and allows the manifestation of a variety of phenotypes from the same genome.The early-life years represent a period of particular susceptibility to epigenetic alteration, as active changes in DNA methylation and histone marks are occurring as part of developmental programs and in response to environmental cues, which notably include psychosocial stimulation and maternal behavior. Memory formation and storage, response to stress in adult life, behavior, and manifestation of neurodegenerative conditions can all be imprinted in the organism by epigenetic modifications that contribute to shape the brain during prenatal or early postnatal life. Moreover, if these epigenetic alterations are preserved in the germ line, changes induced in one generation are likely inherited by future offspring. Programming by transgenerational inheritance thus represents a central mechanism by which environmental conditions may influence disease risk across multiple generations.As novel techniques emerge and as genome-wide profiling of disease-associated methylomes is achieved, epigenetic marks open a new source for biomarker discovery.