Enduring influences of peripubertal stressors on reproductive behavior in female rodents

特定发育阶段的压力会对大脑和行为产生长期影响。 研究发现，特定的压力源，即使是小鼠青春期的短期挑战，也会导致成年后大脑对激素雌二醇和孕酮的反应发生有害变化。 由于这些激素影响所有脊椎动物的广泛行为，因此必须了解仅持续一两天的短暂事件如何对激素反应产生持久的负面影响。 将确定青春期应激源对激素的行为反应的影响持续到成年期多久，将确定它是否推广到另一种啮齿动物物种，并将确定这种强大的影响是否推广到通过独立的细胞信号传导途径起作用的不同免疫挑战。 使用分子和表观遗传学工具，一个新的假设，这种重新编程的反应激素的细胞基础将被测试。 据预测，青春期的压力会导致长期的改变，在调节脑受体的雌二醇，这是介导的甲基化模式的基因的受体的变化，最终重新编程行为反应雌二醇。 这项研究很有价值，因为它解决了所有动物的一个重要问题：短期干扰如何导致长期行为中断？ 这项工作将为各级学生提供独特的培训经验，旨在从事科学和医学事业。 学生参与研究的各个阶段，从假设开发和测试到结果的口头和书面交流。 当学员通过第一手的研究经验学习批判性思维和假设检验的原则时，预计他们将作为未来的教育工作者和医生正式分享，并在社交场合非正式地分享，从而大大增加科学的影响力。

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.