Cholinergic Basal Forebrain Signaling in Body Weight Homeostasis

体重稳态中的胆碱能基底前脑信号传导

• 批准号: 9068353
• 负责人: Alexander Michael Herman
• 金额: $ 1.11万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9068353
• 关键词: Ablation; Accounting; Acetylcholine; Address; Adult; Affect; American; Anorexia; Body Weight; Brain; Brain region; Bulimia; Cardiovascular Diseases; Cause of Death; Cell Death; Cholinergic Receptors; Data; Desire for food; Diabetes Mellitus; Diagonal Band of Broca; Disease; Eating; Eating Disorders; Energy Metabolism; Expenditure; Feeding behaviors; Food Energy; Genetic; Goals; Health; Healthcare; Healthcare Systems; Homeostasis; Hypothalamic structure; Maps; Mediating; Metabolic Diseases; Metabolism; Molecular Profiling; Morbid Obesity; Mus; Neurons; Nicotine; Obesity; Obesity associated disease; Pathogenesis; Pathway interactions; Peptide Signal Sequences; Physiological; Physiology; Play; Population; Prevalence; Process; Prosencephalon; Role; Signal Transduction; System; Techniques; Testing; Tobacco use; United States; Weight Gain; Weight maintenance regimen; acetylcholine receptor agonist; basal forebrain; basal forebrain cholinergic neurons; behavior test; brain cell; cell type; cholinergic; effective therapy; energy balance; feeding; innovation; neural circuit; programs; response; smoking cessation; targeted treatment

DESCRIPTION (provided by applicant): Obesity-associated diseases such as cardiovascular disease and diabetes account for the leading causes of death in the United States. In addition, eating disorders such as anorexia and bulimia nervosa affect millions of people worldwide. Feeding behavior is largely regulated in the brain, which integrates diverse signals from throughout the body in order to modulate the body's response to eat. Perturbations to the brain circuits that regulate this process contribute to the pathogenesis of eating and metabolic disorders. Therefore, fully understanding the brain's role in regulating food intake is essential fr developing effective therapies to treat these disorders. Towards this goal, we have recently discovered that loss of cholinergic neurons from the basal forebrain leads to increased food intake and severe obesity in adult mice. Furthermore, we have shown that these neurons project to, and receive input from, the hypothalamus, a major control center of feeding behavior. Using innovative techniques in genetics, physiology, and behavioral testing, we propose to determine the role of cholinergic basal forebrain signaling on body weight homeostasis. Specifically, we propose to (1) determine the effect of impaired or enhanced cholinergic basal forebrain signaling on food intake, energy expenditure, and feeding- associated peptide signaling, and (2) map, characterize, and mechanistically determine the neuronal brain circuits involved in cholinergic-mediated effects on feeding behavior and body weight homeostasis.

描述（由申请人提供）：在美国，与肥胖相关的疾病，如心血管疾病和糖尿病是导致死亡的主要原因。此外，厌食症和神经性贪食症等饮食失调影响着全世界数百万人。进食行为在很大程度上是由大脑调节的，大脑整合了来自全身的各种信号，以调节身体对进食的反应。对调节这一过程的脑回路的扰动有助于饮食和代谢紊乱的发病机制。因此，充分了解大脑在调节食物摄入中的作用对于开发治疗这些疾病的有效疗法至关重要。为了实现这一目标，我们最近发现，基底前脑胆碱能神经元的丧失导致成年小鼠食物摄入量增加和严重肥胖。此外，我们已经证明，这些神经元投射并接收来自下丘脑的输入，下丘脑是进食行为的主要控制中心。利用遗传学、生理学和行为测试的创新技术，我们建议确定胆碱能基底前脑信号在体重稳态中的作用。具体来说，我们建议(1)确定受损或增强的胆碱能基底前脑信号对食物摄入、能量消耗和摄食相关肽信号的影响；(2)绘制、表征和机制确定参与胆碱能介导的摄食行为和体重稳态效应的神经元脑回路。