International Research Fellowship Program: Stress and Reproduction: Mechanisms and Functions of Acute Stress Effects on Brain Aromatase Activity

该奖项由2009年美国复苏和再投资法案(公法111-5)资助。国际研究奖学金计划使美国科学家和工程师能够在国外进行9至24个月的研究。该项目的奖项提供了联合研究的机会，并利用国外独特或互补的设施、专业知识和实验条件。该奖项将支持莫莉·狄更斯博士与比利时列日大学的雅克·巴尔萨扎特博士合作的为期24个月的研究奖学金。当动物在野外遇到压力源时，直接目标是生存。例如，由于躲避捕食者比繁殖更直接的问题，快速抑制生殖行为通常被认为是对急性应激源的重要适应性反应。然而，当一只动物受到长期的压力时，这种暂时的生殖抑制可能会成为长期的，对动物不利的-S的健康。与应激有关的对生殖的长期抑制对保护工作尤其有问题，理解这种抑制越来越重要，因为物种保护更多地依赖于应激的人类调解，如圈养繁殖、重新引入和易位。为了充分了解慢性应激对生殖行为的影响，必须了解性行为和急性应激之间适应性联系的潜在机制。PI正在与Jacques Balthazart博士合作，利用具有良好特征的日本鹌鹑模型来解决急性应激和生殖行为之间的这种联系，后者为理解日本鹌鹑生殖行为的神经学基础奠定了概念基础。成年雄性日本鸣禽的性行为被睾酮(T)芳构化产生的17β-雌二醇(E_2)迅速激活，初步数据表明，急性束缚应激或皮质酮(CORT)注射会改变芳香酶的活性。该项目的目标是研究这种相互作用，以确定急性应激对芳香酶依赖的生殖行为的机制和功能作用。当这种作用发生时，PI和寄主首先通过测试胁迫或外周注射应激激素后芳香酶活性变化的潜伏期来进行寻址。此外，他们正在测试这个动作发生在哪里，以及这个动作是如何传递到含有芳香酶的大脑区域的。PI和寄主还通过测试假设，即如果压力改变芳香酶活性，依赖芳香酶的生殖行为的变化将与这些变化相对应，来评估该链接的功能。为了验证这一假设，PI和宿主正在跟踪由于急性压力和激素注射而导致的交配行为频率的变化，确定这些变化如何依赖于应激源的严重程度，并评估压力对生殖行为学习的作用。PI和寄主预测，急性应激和相关激素将通过改变雄性鹌鹑视前核芳香酶活性来改变繁殖行为。PI打算利用从这些实验中获得的知识，最终调查长期应激是如何导致生殖行为长期受到抑制的，因为它与保护工作的困难有关。

0910495DickensThis award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).The International Research Fellowship Program enables U.S. scientists and engineers to conduct nine to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad.This award will support a twenty-four month research fellowship by Dr. Molly Dickens to work with Dr. Jacques Balthazart at the University of Liege in Belgium.When an animal encounters a stressor in the wild, the immediate goal is survival. Since escaping a predator, for example, is more an immediate concern than breeding, a quick suppression of reproductive behavior is often thought to be an important adaptive response to an acute stressor. However, when an animal is chronically stressed, this temporary suppression of reproduction can become long-term and detrimental for the animal?s fitness. Chronic stress-related suppression of reproduction is especially problematic for conservation efforts and understanding this suppression is increasingly important as species preservation depends more heavily on stressful human mediation such as captive breeding, reintroduction and translocation. In order to fully understand the chronic stress effects on reproductive behavior, the underlying mechanisms of the adaptive connection between sexual behavior and acute stress must be understood. The PI is addressing this link between acute stress and reproductive behavior utilizing the well-characterized Japanese quail model in collaboration with Dr. Jacques Balthazart, who established the conceptual groundwork for understanding the neurological basis of reproductive behaviors in Japanese quail. In adult male Japanese quail, sexual behaviors are activated rapidly (within a minute) by 17 beta-estradiol (E2) derived from aromatization of testosterone (T) and preliminary data suggest that acute restraint stress or injection of corticosterone (CORT), alters activity of the aromatase enzyme. The goal of the project is to investigate this interaction to determine the mechanistic and functional role of acute stress acting on aromatase-dependent reproductive behaviors. The PI and host are first addressing when this action occurs by testing the latency of changes in aromatase activity following stress, or peripheral injections of stress hormones. In addition, they are testing where this action occurs and how the action is communicated to aromatase-containing brain regions. The PI and host are also evaluating the functionality of the link by testing the hypothesis that if stress alters aromatase activity then changes in aromatase-dependent reproductive behaviors will correspond to these alterations. To test this hypothesis, the PI and host are tracking changes in frequency of copulatory behaviors due to acute stress and hormone injections, determining how the changes depend on degree of stressor severity, and evaluating the role of stress on learning of reproductive behaviors. The PI and host predict that acute stress and the related hormones will alter reproductive behavior through changes in aromatase activity in the preoptic nucleus of male quail. The PI intends to use the knowledge gained from these experiments to eventually investigate how chronic stress leads to long-term suppression of reproductive behavior as it pertains to difficulties with conservation efforts.