Role of Serotonin in Sympathetic Function

血清素在交感功能中的作用

• 批准号: 6895202
• 负责人: KARIE E SCROGIN
• 金额: $ 22.2万
• 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/6895202
• 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.

在大量失血量之后，通常有助于维持血压的补偿性神经反应突然失败，导致血管舒张，深度心动过缓和威胁生命的低血压。介导这种交感反应的中枢神经系统机制尚不清楚。对这种机制的更全面的理解可能会导致对循环休克和其他疾病的新型治疗方法，并具有异常激活交感反射的激活，例如心脏的腹部心脏壁的心肌梗死，与主动脉狭窄或神经源性促进相关的劳累晕厥。在 由于麻醉对自主功能的影响，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伴随着意识大鼠严重失血的突然流失中的突然丧失。具体而言，研究旨在鉴定5-羟色胺的来源和在出血期间介导交感神经戒断的受体群体。提出的实验涉及 经典生理模型的新颖用途来研究离散后脑神经元和受体群体在不动理大鼠中交感神经功能中的作用。结合神经元图与神经元表型和功能的免疫组织化学标记的解剖研究将用于确定与交感反射相关的5-羟色胺的来源和投影位点。该提案中概述的新技术将有助于确定一般和尤其是在交感神经调节中，尤其是在交感神经调节上的后脑血清素能细胞和受体功能，这一目标迄今为止受到了麻醉对annesthesia对出血反应和血清素能反应的混杂影响的阻碍 功能。