Stress during particular developmental stages has long-term effects on brain and behavior. It was discovered that particular stressors, even very short-duration challenges during the pubertal period in mice cause deleterious changes in the brain's response to the hormones, estradiol and progesterone, in adulthood. Because these hormones influence such a wide range of behaviors in all vertebrate animals, it is essential to understand how a transient event lasting only a day or two can have an enduring negative influence on hormonal response. It will be determined how long into adulthood the effects of pubertal stressors on behavioral response to hormones endure, it will be determined if it generalizes to another rodent species, and it will be determined if this robust effect generalizes to a different immune challenge that works through an independent cellular signaling pathway. Using molecular and epigenetic tools, a novel hypothesis for the cellular underpinnings of this reprogramming of response to hormones will be tested. It is predicted that pubertal stressors cause long-term alteration in regulation of brain receptors for estradiol, and that this is mediated by changes in methylation patterns of the gene for the receptor, ultimately reprogramming behavioral response to estradiol. This research is valuable, because it addresses an important problem for all animals; how does a short-term perturbation cause long-term disruption in behavior? This work will provide unique training experiences for students at all levels aiming for careers in science and medicine. Students are involved at all stages of research from hypothesis development and testing to oral and written communication of results. When trainees learn principles of critical thinking and hypothesis testing through first-hand research experience, it is anticipated that they will share it formally as future educators and physicians and informally in social situations, thereby dramatically increasing the reach of the science.
