Factors mediating effects of pubertal stressors on adult response to hormones

青春期应激源对成人激素反应影响的调节因素

• 批准号: 8091824
• 负责人: Jeffrey D Blaustein
• 金额: $ 23.17万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-15 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8091824
• 关键词: Acute; Adolescence; Adolescent; Adult; Age; Animal Model; Animals; Anti-Anxiety Agents; Anti-Inflammatory Agents; Anti-inflammatory; Antidepressive Agents; Anxiety; Area; Behavior; Behavioral; Brain; Cell physiology; Corticosterone; Data; Development; Dose; Endotoxins; Estradiol; Female; Future; Goals; Health; Hormonal; Hormones; Immune; Interleukin-10; Interleukin-6; Knowledge; Lead; Lipopolysaccharides; Long-Term Effects; Mediating; Mental Depression; Mental Health; Mental disorders; Mission; Modeling; Mus; National Institute of Mental Health; Neuroendocrinology; Ovarian hormone; Personality Disorders; Physiological; Plasma; Poly I-C; Predisposition; Process; Psychopathology; Puberty; Reproductive Behavior; Research; Shipping; Ships; Staging; Stress; Study models; TNF gene; Testing; Time; Viral; Woman; Work; addiction; behavior influence; cytokine; innovation; mimetics; novel; research study; response; stressor

DESCRIPTION (provided by applicant): There are gaps in understanding of the influences of stressors during puberty on the later development of psychiatric disorders in adulthood. It has recently been discovered that particular stressors during the pubertal period in female mice result in an enduring alteration in behavioral response to ovarian hormones, including behaviors related to depression and anxiety. Because of the importance of this developmental stage in adult behaviors related to mental health that are regulated by the ovarian hormones, the acute physiological effects of particular pubertal stressors that do or do not influence behavioral response to ovarian hormones in adulthood will be tested. The long-term goal of this project is to discover the mechanisms by which particular stressors during a narrow, pubertal period alter adult, behavioral responses to ovarian hormones using animal models. The central hypothesis is that particular stressors during a well-defined, pubertal period induce acute, physiological changes that then result in an alteration in behavioral responses to ovarian hormones, including the response to estradiol on depression- and anxiety-like behaviors. The rationale for this prediction is that particular pubertal stressors during a narrowly defined period dramatically alter the effects of ovarian hormones on a variety of behaviors, and there must be differences in the acute physiological responses of the animals to these stressors at these times. We have observed elimination of, or alteration in, behavioral responses to estradiol in female mice exposed to particular stressors during puberty. This is consistent with work by others that the pubertal period is a critical time in the development of adult behavioral response to ovarian hormones, but the finding that a transient stressor at this time can have permanent effects on behavioral response to ovarian hormones is novel. In the specific aim, hypotheses concerning the cellular processes that are responsible for the alteration in hormonal response in adulthood will be tested. Specifically the relationship of immune challenge-induced sickness behavior, thermoregulatory responses, and changes in plasma and brain cytokines to the altered behavioral response to ovarian hormones will be assessed. These experiments will lead to direct tests of the mechanisms responsible for the altered behavioral response to ovarian hormones that endures into adulthood. This research will advance the field of Behavioral Neuroendocrinology by identifying influences during the pubertal period on adult behavioral response to ovarian hormones and the mechanisms of these influences. The research is innovative, because it investigates the causes of enduring influences of stressors during a well-defined, pubertal stage of development on behavioral response specifically to ovarian hormones. This work is significant, because it will serve as a model for studies of other mental health-related endpoints that are influenced by estradiol, including addiction and other personality and psychiatric disorders. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to mental health, because particular stressors during the pubertal/adolescent period decrease response to ovarian hormones on mental health-related behaviors in adulthood. The research is relevant to the mission of NIMH, because it will provide understanding of the mechanisms by which some pubertal stressors influence adult behavioral response to ovarian hormones.

描述（由申请人提供）：对于青春期压力源对成年期精神障碍后期发展的影响的理解存在差距。最近发现，雌性小鼠青春期期间的特定应激源导致对卵巢激素的行为反应发生持久改变，包括与抑郁和焦虑相关的行为。由于这一发育阶段在与卵巢激素调节的心理健康相关的成人行为中的重要性，将测试特定青春期应激源的急性生理效应，这些应激源是否影响成年期对卵巢激素的行为反应。这个项目的长期目标是发现在一个狭窄的青春期特定的应激源改变成年的机制，卵巢激素使用动物模型的行为反应。核心假设是，在明确定义的青春期期间，特定的压力源诱导急性生理变化，然后导致对卵巢激素的行为反应发生改变，包括对雌二醇对抑郁和焦虑样行为的反应。这一预测的基本原理是，在一个狭窄的定义期间，特定的青春期应激源显着改变卵巢激素对各种行为的影响，并且动物在这些时间对这些应激源的急性生理反应一定存在差异。 我们观察到雌性小鼠在青春期暴露于特定的压力源时，对雌二醇的行为反应会发生消除或改变。这与其他人的研究结果一致，即青春期是成年人对卵巢激素的行为反应发展的关键时期，但发现此时的短暂压力源可能对卵巢激素的行为反应产生永久性影响是新颖的。在具体的目标，假设有关的细胞过程，负责在成年期激素反应的变化将进行测试。具体而言，将评估免疫激发诱导的疾病行为、体温调节反应以及血浆和脑细胞因子变化与卵巢激素行为反应改变的关系。这些实验将直接测试对卵巢激素的行为反应改变的机制，这种反应持续到成年。 这项研究将通过确定青春期对卵巢激素的成年行为反应的影响以及这些影响的机制来推进行为神经内分泌学领域。这项研究是创新的，因为它调查了在发育的明确的青春期阶段，压力源对卵巢激素的行为反应产生持久影响的原因。这项工作意义重大，因为它将作为研究雌二醇影响的其他心理健康相关终点的模型，包括成瘾和其他人格和精神障碍。 公共卫生相关性：这项研究与心理健康有关，因为青春期/青少年时期的特定压力源会降低成年后对卵巢激素对心理健康相关行为的反应。这项研究与NIMH的使命相关，因为它将提供一些青春期应激因素影响成年人对卵巢激素的行为反应的机制的理解。