Non-genetic programming of adult emotional behavior by the grandmother

Weill Medical Coll Of Cornell Univ, New York NY

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Abstract

DESCRIPTION (provided by applicant): Maternal malnutrition, infection, stress, and even mutations can perturb the gestational environment, resulting in increased risk for offspring to develop behavioral abnormalities in both human and animal models. We reported the gestational effect of the inactivation of the maternal 5-HT1A receptor (R) in mice, manifested as anxiety and increased stress responsiveness in the offspring. The consequences of these maternal conditions are often not limited to the first generation, and have actually been found to alter the behavior of the grandchildren. Our recent data show that the anxiety-inducing effect of maternal 5-HT1AR deficit is extended to the F2 generation (grandchildren). Although such intergenerational non-genetic inheritance of behavior increases the incidence of neuropsychiatric disease in the population, the underlying mechanism by which this occurs is essentially unknown. Using embryo transfer and whole genome epigenetic analysis, we study how the behavioral and epigenetic effects of adverse gestational environment propagate to two consecutive generations of offspring.