ACTIVITY OF BRAINSTEM NEURONS

描述(逐字摘自申请者摘要)：流行病学数据显示 肥胖与患高血压的风险增加有关。这个 这种频繁联系背后的病理生理过程很差。 明白了。食欲素A和B是最近分离到的两个多肽，表达于 大鼠下丘脑外侧区神经元的数量。其上的多肽 脑室注射增加了啮齿动物的食物消耗。食欲素 A免疫反应阳性纤维投射到大鼠脑干区 包括延髓头端腹外侧核(RVLM)，孤束核 迷走神经束、疑核和迷走神经背侧运动核 对自主神经的直接控制。RVLM中OrxA-LI纤维的存在 增加了这种多肽也可能参与延髓的可能性 调节交感神经向脊髓的流出。我们的初步研究 结果显示，脑池内或脑室内微量注射食欲素A和B RVLM可提高麻醉大鼠的血压和心率。在这 续期申请时，将采用跨专业的方法测试 食欲素A和B可能与RVLM神经元相互作用并增强 交感神经在大鼠体内流出。第一，类食欲素的分布 将描述大鼠大脑中的免疫反应性。第二，影响 RVLM区微量注射食欲素A或B对血压和心脏的影响 清醒大鼠的比率将被评估。第三，整个细胞贴片记录将是 由脑干-脊髓标本的RVLM神经元或冠状突起制成 脑干切片。记录的神经元将被标记为路西法黄色和 后来进行了PNMT处理-免疫反应用于鉴定目的。这个 增食欲素A或B对RVLM神经元电活动的影响 从离子和信号转导机制方面进行了研究。超重和 高血压是美国的两大健康问题。鉴定 可能的递质和连接下丘脑和 自主神经系统将是我们理解的一个重大进步 这些疾病背后的调控机制。

DESCRIPTION (Verbatim from Applicant's abstract): Epidemiological data show that obesity is associated with an increased risk of hypertension. The pathophysiological processes underlying this frequent association are poorly understood. Orexin A and B are two recently isolated peptides expressed in a population of neurons in the rat lateral hypothalamus. The peptide upon intraventricular injection increases food consumption in rodents. Orexin A-immunoreactive (ORXA-LI) fibers project to areas of the rat brainstem including the rostral ventrolateral medulla (RVLM), the nucleus of the solitary tract, nucleus ambiguous and the dorsal motor nucleus of the vagus that provide direct control of autonomic neurons. The presence of ORXA-LI fibers in the RVLM raises the possibility that the peptide may also be involved in the medullary regulation of the sympathetic outflow to the spinal cord. Our initial study shows that orexin A and B injected intracisternally or microinjected into the RVLM increased blood pressure and heart rate in anesthetized rats. In this renewal application, a multidisciplinary approach will be employed to test the hypothesis that orexin A and B may interact with RVLM neurons and enhance sympathetic outflow in the rat. First the distribution of orexin-like immunoreactivity in the rat brain will be characterized. Second the effects of orexin A or B by microinjection to the RVLM area on blood pressure and heart rate in awake rats will be assessed. Third, whole cell patch recordings will be made from RVLM neurons of brainstem-spinal cord preparations or coronal brainstem slices. Recorded neurons will be labeled with Lucifer yellow and later processed for PNMT-immunoreactivity for identification purposes. The effects of orexin A or B on the electrical activity of RVLM neurons will be studied with respect to ionic and signal transduction mechanism. Overweight and hypertension are two major health problems in the United States. Identification of the putative transmitters and the circuitry linking the hypothalamus to the autonomic nervous system will be a significant improvement in our understanding of the regulatory mechanisms underlying these disorders.