NEUROENDOCRINE REGULATION OF THE STRESS RESPONSE

应激反应的神经内分泌调节

• 批准号: 2628910
• 负责人: JAMES I KOENIG
• 金额: $ 14.89万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-20 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2628910
• 关键词: glutamates; hormone regulation /control mechanism; hypoglycemia; hypothalamic pituitary adrenal axis; immunocytochemistry; in situ hybridization; insulin; kainate; laboratory rat; neuroendocrine system; neurotransmitter receptor; paraventricular nucleus; radioimmunoassay; secretion; stress

DESCRIPTION (Applicant's Abstract): Stress, either of physical or psychological origin, has been implicated as a trigger for a number of devastating autoimmune and neuropsychiatric disorders, such as lupus erythematosus, depression, and schizophrenia. While we have a firm understanding of the physiology of the final common effectors involved in the stress response, i.e., corticotropin-releasing hormone and vasopressin, our knowledge of brain mechanisms activating the hypothalamic-pituitary-adrenal axis is more limited. Clearly, the glucocorticoids have powerful consequences associated with their hypersecretion during and after stress. However, the underlying neural mechanisms providing input to the neurons of the paraventricular nucleus are the substrates of neuropsychiatric illness. A more detailed understanding of the molecular and cellular relationships between neurotransmitters and neuromodulators in the regulation of hypothalamic-pituitary-adrenal axis secretions may provide keys to unlocking disorders, such as depression or schizophrenia or discoveries that may lead to new therapeutics for these disorders. Glutamate is the most abundant excitatory neurotransmitter in the neuroendocrine axis, and has been implicated in the etiology of schizophrenia, yet the physiological role of this excitatory amino acid transmitter is poorly understood in the regulation of the hypothalamic-pituitary-adrenal axis. One of the aims of the proposed studies is to characterize the molecular and cellular events elicited by excitatory amino acid receptor activation in the control of the secretions of the hypothalamic-pituitary-adrenal axis. Hypoglycemia, a well-characterized and readily controllable "metabolic stress," precipitates excitatory amino acid release in the brain. Consequently, another aim of these investigations is to employ molecular and neuroendocrinological techniques to explore the participation of excitatory amino acid receptor activation in the hypothalamic-pituitary-adrenal axis during hypoglycemia. These studies aim to reveal important new information about the regulation of stress hormone secretion by glutamate and may be significant in better understanding brain mechanisms in neuropsychiatric and other stress-related disorders.

描述（申请人的摘要）：压力，无论是身体还是 心理起源已被牵涉到许多触发因素 毁灭性的自身免疫性和神经精神疾病，例如狼疮 红斑，抑郁和精神分裂症。 虽然我们有一个公司 了解最终涉及的最终共同效应子的生理学 压力反应，即皮质激素释放激素和加压素的压力反应， 我们对大脑机制激活的知识 下丘脑 - 垂体 - 肾上腺轴更加有限。 显然， 糖皮质激素具有与其相关的强大后果 压力期间和之后的过度分泌。 但是，基础神经 提供向室核神经元输入的机制是 神经精神疾病的底物。 更详细的理解 神经递质与细胞的分子关系 下丘脑 - 垂体 - 肾上腺轴调节中的神经调节剂 分泌物可能为解锁疾病（例如抑郁症或 精神分裂症或可能导致这些新疗法的发现 疾病。 谷氨酸是最丰富的兴奋性神经递质 神经内分泌轴，并与 精神分裂症，但这种兴奋性氨基酸的生理作用 在调节中，发射器对 下丘脑 - 垂体 - 肾上腺轴。 提议的目标之一 研究是为了表征由 兴奋性氨基酸受体激活分泌物 下丘脑 - 垂体 - 肾上腺轴的 低血糖， 特征良好且容易控制的“代谢应力”，沉淀 兴奋性氨基酸在大脑中释放。 因此，另一个目标 这些研究是采用分子和神经内分泌学 探索兴奋性氨基酸受体参与的技术 低血糖期间下丘脑 - 垂体 - 肾上腺轴的激活。 这些研究旨在揭示有关法规的重要新信息 谷氨酸的胁迫激素分泌，可能在更好的情况下显着 了解神经精神病学和其他压力有关的大脑机制 疾病。