Abstract: Takeshita, et.al.

Epigenetic programming of adrenal androgens by early life adversity and its role in modulating the HPA axis

Drs. Rafaela Takeshita (Department of Anthropology, Kent State University), Chris Faulk (University of Minnesota), Joe Simmons (MD Anderson Cancer Center) and Sarah Neal (MD Anderson Cancer Center)

Early life adversity (ELA) can disrupt infant development and may lead to long-lasting impacts on their ability to cope with adverse situations. Studies animal models have shown that infant neglect or hand-reared individuals can result in abnormal behaviors, impaired cognitive performance, heightened anxiety and difficulties with coping mechanisms due to impairment of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the stress response. While many studies have investigated the relationship between cortisol and ELA, recent studies on stress have focused on the ratio of cortisol to the adrenal androgen dehydroepiandrosterone (DHEA) as a proxy to evaluate the HPA axis. DHEA, a cortisol antagonist, crosses the blood-brain barrier, and it is known for its neuroprotection and neurogenesis effects in the brain. Consequently, disruption in the HPA axis early in life may impact brain development due to the imbalance between cortisol and DHEA secretion. The goal of this project is to investigate DHEA as potential mediator of ELA, as well as the epigenetic mechanisms that moderate DHEA activity in the brain of maternally deprived individuals. The results will reveal whether central and peripheral DHEA levels are affected by ELA, and it will identify the possible epigenetic pathways that mediate the long-lasting effects of ELA in the HPA axis.