Thirst Deficits in Rat Model of Aging

描述（由申请人提供）：脱水涉及身体水分的损失。脱水引发反射和行为反应，减缓水分流失的速度，最终恢复身体水分。为了激活适当的稳态反应，中枢神经系统必须接收和整合来自监测体液状态的专门受体的多种类型的感觉输入。这种传入信息包括由血液携带的体液信号和由神经携带的血管受体产生的神经信号。水平衡失调，包括脱水，是老年人的主要健康问题。老年人的脱水是由于肾脏保持体内水分的能力受损，口渴的感觉受损。对于老年人肾功能和心血管功能的损害以及这些机制对已知伴随老年的相对脱水状态的贡献有一些了解。然而，很少有人知道在老年人控制的行为机制，参与体积稳态。关于激素和神经信号机制刺激老年人饮水的能力，人们知之甚少。本提案建立在申请人先前对流体相关的传入信号和中央处理的研究的基础上。拟议的研究将采用生理学，药理学，行为学和细胞技术在大鼠中，允许调查相互作用的激素（血管紧张素，心房利钠肽）和神经（血压/容量）传入信号，控制低血容量和渗透性口渴的大鼠模型老化。这些实验将产生关于维持和恢复衰老动物体液稳态的基本生理机制的重要新信息。增加对这些神经生物学过程的理解将有助于健康的正常人暴露于生理（运动）和环境（热）的挑战和某些类型的患者与病理条件有关的液体平衡（高血压，充血性心力衰竭），以及老年人的福祉。

DESCRIPTION (provided by applicant): Dehydration involves loss of body water. Dehydration elicits reflexive and behavioral responses that slow the rate of water loss and ultimately restore body water. In order for appropriate homeostatic responses to be activated, the central nervous system must receive and integrate multiple types of sensory input from specialized receptors that monitor the status of body fluids. This afferent information includes humoral signals carried by the blood and neural signals arising from vascular receptors carried by nerves. Disturbances of water balance, including dehydration, are major health problems in the elderly. Dehydration in the elderly results from impairments in the ability of the kidney to retain water in the body, and impaired sensations of thirst. There is some understanding regarding impairments in renal and cardiovascular function in the elderly and the contributions of these mechanisms to the relative state of dehydration that is known to accompany old age. However, little is known in the elderly about control of the behavioral mechanisms that are involved in volume homeostasis. There is remarkably little knowledge about the ability of hormonal and neural signaling mechanisms to stimulate water drinking in the elderly. The present proposal builds upon the applicant's prior investigations of fluid-related afferent signaling and central processing. The proposed research will employ physiological, pharmacological, behavioral, and cellular techniques in the rat that permit the investigation of interactive hormonal (angiotensin, atrial natriuretic peptide) and neural (blood pressure/volume) afferent signals that control hypovolemic and osmotic thirst in a rat model of aging. These experiments will generate important new information about basic physiological mechanisms that maintain and restore body fluid homeostasis in aging animals. Increased understanding of these neurobiological processes will contribute to the well-being of normal individuals exposed to physiological (exercise) and environmental (heat) challenges and of certain types of patients with pathological conditions related to fluid balance (hypertension; congestive heart failure), as well as the well being of the elderly.