Functional mapping of thirst circuits in the aging mouse brain

衰老小鼠大脑口渴回路的功能图谱

• 批准号: 9761333
• 负责人: Heeun Jang
• 金额: $ 6.16万
• 依托单位: BUCK INSTITUTE FOR RESEARCH ON AGING
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2022-03-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9761333
• 关键词: Acute; Address; Age; Aging; Angiotensin II; Behavior; Behavioral; Blood; Blood Circulation; Blood specimen; Body Fluids; Brain; Brain imaging; Brain region; Cell Nucleus; Cognitive; Data; Dehydration; Diabetes Mellitus; Elderly; Esthesia; Exhibits; Exposure to; FOS gene; Fiber; Fluid Balance; Fracture; Glutamates; Health; Heart failure; Homeostasis; Hormones; Hydration status; Hypesthesia; Hypothalamic structure; Impaired cognition; Impairment; Individual; Intake; Intercellular Fluid; Intervention; Kidney Failure; Life; Liquid substance; Maintenance; Measures; Monitor; Motivation; Mus; Negative Valence; Neurons; Neurosecretory Systems; Organism; Osmolalities; Osteoporosis; Output; Pattern; Photometry; Physiological; Plasma; Population; Rehydrations; Risk; Rodent Model; Site; Sodium Chloride; Stimulus; Structure; Subfornical Organ; Techniques; Testing; Thirst; Time; Unconscious State; Urine; Water; Water consumption; Work; age related; awake; behavior change; clinically significant; cohort; drinking; drinking behavior; drinking water; experimental study; feeding; high risk; image guided; in vivo; mortality; mouse model; neural circuit; optogenetics; relating to nervous system; response; sensory input; therapeutic target; willingness

PROJECT SUMMARY/ ABSTRACT Fluid homeostasis, the maintenance of volume and osmolality in blood and interstitial fluid, is essential for life. Aging involves breakdown of fluid homeostasis, and is often accompanied by reduced thirst and drinking behavior. As a result, dehydration is one of the major health risks in older individuals, exposing them to higher risk for developing diabetes mellitus, heart or kidney failure, or reduced or loss of consciousness, and thereby greatly increasing their mortality. However, the mechanism by which thirst and drinking behavior changes with advancing age is very poorly understood. Fluid homeostasis is primarily regulated by a structure in hypothalamus called the subfornical organ (SFO), which monitors the state of fluid balance via direct access to systemic circulation. Recently, a specific population of neurons within the SFO was shown to be both necessary and sufficient for regulating drinking behavior. Here I propose to systematically investigate how the thirst circuit changes with aging, using fiber photometry and optogenetic techniques in awake behaving mice. Understanding how the function of the thirst circuit changes with age will expand our ability to develop interventions and treatment for fluid imbalance and related illnesses in the elderly.

项目摘要/摘要 液体稳态是血液和间质液中体积和渗透压的维持，对生命至关重要。 衰老涉及液体体内平衡的分解，并且经常伴有减少和饮酒 行为。结果，脱水是老年人的主要健康风险之一，使他们暴露于更高 患糖尿病，心脏或肾衰竭或降低或意识的风险，从而 大大增加了他们的死亡率。但是，口渴和饮酒行为的机制随着 促进年龄的理解很差。流体稳态主要由 下丘脑称为副构造器官（SFO），该器官通过直接访问来监视流体平衡状态 全身循环。最近，SFO内的特定神经元群体被证明是 必要且足以调节饮酒行为。在这里，我建议系统地研究 口渴的回路随着衰老而变化，使用纤维光度法和光遗传技术在醒着的行为小鼠中。 了解口渴回路随着年龄的变化如何变化将扩大我们发展的能力 老年人对液体失衡和相关疾病的干预措施和治疗。