ACTIVITY OF BRAINSTEM NEURONS

描述（逐字摘自申请人摘要）：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很差 明白了。食欲素 A 和 B 是最近分离的两种肽，在 大鼠下丘脑外侧部的神经元群。上的肽 脑室内注射会增加啮齿动物的食物消耗。食欲素 A-免疫反应性 (ORXA-LI) 纤维投射到大鼠脑干区域 包括头端腹外侧延髓 (RVLM)、孤立神经核 束、模糊核和迷走神经的背运动核提供 直接控制自主神经元。 RVLM 中存在 ORXA-LI 纤维 提出了肽也可能参与髓质的可能性 调节交感神经向脊髓的流出。我们的初步研究 显示食欲素 A 和 B 注射到脑池内或显微注射到 RVLM 会增加麻醉大鼠的血压和心率。在这个 更新申请，将采用多学科方法来测试 假设食欲素 A 和 B 可能与 RVLM 神经元相互作用并增强 大鼠的交感神经流出。首先是类食欲素的分布 将表征大鼠大脑中的免疫反应性。二、效果 通过向 RVLM 区域显微注射食欲素 A 或 B 对血压和心脏的影响 将评估清醒大鼠的比率。第三，全细胞贴片记录将 由脑干脊髓制剂或冠状病毒的 RVLM 神经元制成 脑干切片。记录的神经元将被标记为路西法黄色和 随后进行 PNMT 免疫反应性处理以用于识别目的。的 食欲素 A 或 B 对 RVLM 神经元电活动的影响 研究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。鉴定 假定的发射器和连接下丘脑与 自主神经系统将显着提高我们的理解力 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.