Role of Serotonin in Sympathetic Function

血清素在交感功能中的作用

• 批准号: 6683060
• 负责人: KARIE E SCROGIN
• 金额: $ 21.72万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6683060
• 关键词: autoradiography; baroreceptors; cardiovascular function; central nervous system; consciousness; decerebration; hemorrhage; high performance liquid chromatography; immunocytochemistry; laboratory rat; microinjections; neural transmission; neuroanatomy; neuronal transport; neurons; neuropharmacology; neurophysiology; rhombencephalon; serotonin; serotonin receptor; sympathetic nervous system; western blottings

Following a critical amount of blood loss, compensatory neural responses that normally help maintain blood pressure suddenly fail, causing vasodilation, profound bradycardia and life-threatening hypotension. The central nervous system mechanisms that mediate this sympatholytic response are unknown. A more comprehensive understanding of such mechanisms could lead to novel treatments for circulatory shock and other disorders with aberrant activation of sympatholytic reflexes such as myocardial infarct of the inferoposterior wall of the heart, exertional syncope associated with aortic stenosis or neurogenic syncope. In vivo models devised to examine these responses have been limited due to the effects of anesthesia on autonomic function. The objective of this proposal is to elucidate the role of hindbrain serotonergic cellular- and receptor mediated mechanisms in the sudden loss of sympathetic activity that accompanies severe blood loss in the conscious rat. Specifically, studies have been designed to identify the source of serotonin and the receptor populations that mediate sympathetic withdrawal during hemorrhage. The proposed experiments involve novel uses of classic physiological models to study the role of discrete hindbrain neuronal and receptor populations in the regulation of sympathetic function in unanesthetized rats. Anatomical studies that combine neuronal tract tracing with immunhistochemical markers of neuronal phenotype and function will be used to determine the source and projection site of serotonin involved in sympathetic reflexes. The novel techniques outlined in this proposal will help to determine hindbrain serotonergic cellular and receptor function on sympathetic regulation in general and on hemorrhage responses in particular, a goal which has, until now, been hampered by the confounding influence of anesthesia on hemorrhage responses and serotonergic function.

在失血量达到临界值后，通常有助于维持血压的代偿性神经反应突然失效，导致血管舒张、严重心动过缓和危及生命的低血压。介导这种交感神经反应的中枢神经系统机制尚不清楚。对这些机制的更全面的了解可能会导致对循环性休克和其他交感神经反射异常激活的疾病（如心脏下后壁心肌梗死、与主动脉瓣狭窄或神经源性晕厥相关的劳力性晕厥）的新治疗。在 由于麻醉对自主神经功能的影响，设计用于检查这些反应的体内模型受到限制。该提案的目的是阐明后脑血清素能细胞和受体介导的机制在意识大鼠伴随严重失血的交感神经活性突然丧失中的作用。具体来说，研究的目的是确定血清素的来源和出血期间介导交感神经退缩的受体群。拟议的实验包括 新用途经典生理模型来研究离散后脑神经元和受体群在未麻醉大鼠交感功能调节中的作用。将神经元束示踪与神经元表型和功能的免疫组织化学标记相结合的解剖学研究将用于确定参与交感神经反射的血清素的来源和投射部位。该提案中概述的新技术将有助于确定后脑血清素细胞和受体对交感神经调节的一般功能，特别是对出血反应的功能，迄今为止，这一目标一直受到麻醉对出血反应和血清素能的混杂影响的阻碍。 功能。