ACTIVITY OF BRAINSTEM NEURONS

描述（来自申请人摘要的逐字描述）：流行病学数据显示 肥胖与高血压风险增加有关。的 这种频繁关联背后的病理生理过程 明白增食欲素A和B是两种最近分离的肽，它们表达在一种表达载体中。 大鼠外侧下丘脑的神经元群体。肽在 脑室内注射增加啮齿动物的食物消耗。食欲素 A-免疫反应（ORXA-LI）纤维投射到大鼠脑干的区域 包括延髓头端腹外侧区（RVLM），孤束核， 迷走神经束、疑核和背侧运动核， 自主神经元的直接控制。RVLM中存在ORXA-LI纤维 提出了这种肽也可能参与骨髓 调节交感神经流出到脊髓。我们最初的研究 显示了脑池内注射或微注射到脑内的食欲素A和B， RVLM增加麻醉大鼠的血压和心率。在这 续期申请，将采用多学科方法来测试 假设食欲素A和B可能与RVLM神经元相互作用， 大鼠交感神经流出。首先是食欲素样蛋白的分布 将表征大鼠脑中的免疫反应性。第二，影响 通过向RVLM区域微量注射食欲素A或B对血压和心脏的影响 将评估清醒大鼠中的速率。第三，整个细胞补丁记录将是 由脑干-脊髓制备物或冠状面的RVLM神经元制成 脑干切片记录的神经元将用荧光黄标记， 随后进行PNMT免疫反应性处理以用于鉴定目的。的 食欲素A或B对RVLM神经元电活动的影响将被 研究了离子和信号转导机制。超重和 高血压是美国的两大健康问题。识别 下丘脑和大脑皮层之间的联系 自主神经系统将是我们理解的一个重大进步 这些疾病背后的调节机制。

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.