The cellular memory of early life adversity

Weill Medical Coll Of Cornell Univ, New York NY

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Abstract

Abstract Gestational and early postnatal adverse experiences, because of their psychopathological consequences later in life, represent a significant burden for the affected individual and society. We identified an epigenetic motif at over two thousand neuronal enhancers that, via dynamic switching between the active to inactive states, control gene expression. The stochastic balance between the two states is altered by early life adversity in a subpopulation of neurons, resulting in abnormal neuronal functioning. We will test the hypothesis that permanent changes in the methylation state of the identified enhancer ?switches? represent the ?cellular memory? of early life adverse experiences. Adversity-induced epigenetic changes increase the size and/or activity of neurons amenable for recruitment during behavioral tasks, that in turn, increase the responsiveness of the circuit to novel/stressful stimuli, manifested as exaggerated fear reaction/anxiety later in life. Besides of the theoretical implications (coding environmental effects via binary epigenetic switches), our work has translational significance. The sensitivity of DNA methylation based switches (due to their metastability), compared to the rest of the epigenetically more stable genome, provides an opportunity for their selective manipulation to mitigate the adverse effects of ELA.