NEUROENDOCRINE REGULATION OF THE STRESS RESPONSE

应激反应的神经内分泌调节

• 批准号: 2905977
• 负责人: JAMES I KOENIG
• 金额: $ 15.28万
• 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/2905977
• 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）：身体或身体上的压力 心理起源，被认为是许多疾病的触发因素 毁灭性的自身免疫和神经精神疾病，例如狼疮 红斑狼疮、抑郁症和精神分裂症。 虽然我们有坚定的 了解参与的最终共同效应器的生理学 应激反应，即促肾上腺皮质激素释放激素和加压素， 我们对激活大脑机制的了解 下丘脑-垂体-肾上腺轴更为有限。 显然， 糖皮质激素具有与其相关的强大后果 应激期间和应激后分泌过多。 然而，潜在的神经 向室旁核神经元提供输入的机制是 神经精神疾病的基础。 更详细的了解 神经递质和细胞之间的分子和细胞关系 调节下丘脑-垂体-肾上腺轴的神经调节剂 分泌物可能提供解锁疾病的钥匙，例如抑郁症或 精神分裂症或可能为这些疾病带来新疗法的发现 失调。 谷氨酸是体内最丰富的兴奋性神经递质 神经内分泌轴，并与病因学有关 精神分裂症，但这种兴奋性氨基酸的生理作用 发射机的调节知之甚少 下丘脑-垂体-肾上腺轴。 拟议的目标之一 研究的目的是表征由以下因素引起的分子和细胞事件 兴奋性氨基酸受体激活控制分泌 下丘脑-垂体-肾上腺轴。 低血糖症， 特征明确且易于控制的“代谢应激”沉淀 大脑中兴奋性氨基酸的释放。 因此，另一个目标 这些研究是利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监管的重要新信息 谷氨酸盐分泌应激激素，可能对更好地发挥作用具有重要意义 了解神经精神学和其他压力相关的大脑机制 失调。