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Parsing the central control of thirst and hunger using a rat model of diabetes insipidus

使用尿崩症大鼠模型解析口渴和饥饿的中枢控制

基本信息

批准号：
10684254
负责人：
Derek Daniels
金额：
$ 53.57万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-17 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10684254
关键词：
Address Agonist Area Behavior Behavior Control Behavioral Body Fluids Brain Brattleboro Rats Cardiovascular system Cell Separation Cells Central Diabetes Insipidus Compensation Consumption Data Dehydration Diabetes Insipidus Diabetes Mellitus Disease Diuresis Eating Failure Feeding behaviors Fluid Balance GLP-I receptor Genotype Health Homeostasis Hunger Hypertension Intake Laboratories Lead Ligands Liquid substance Long-Evans Rats Maintenance Malnutrition Modeling Motivation Mutation Neural Pathways Nucleotides Obesity Pathway interactions Phenotype Polydipsia Polyuria Population Rattus Residual state Rodent Model Satiation Series Signal Transduction Site Source Structure System Testing Thirst Tracer Vasopressins Water Water consumption antagonist diabetic rat drinking energy balance feeding genetic manipulation glucagon-like peptide 1 hindbrain motivated behavior neural neural circuit neuroregulation novel strategies pharmacologic preoptic nucleus preproglucagons prevent receptor binding response restoration

项目摘要

Project Summary: Feeding and drinking are essential behaviors for the maintenance of energy and fluid homeostasis. Failure to maintain energy balance causes obesity or malnutrition and perturbations in fluid balance cause dehydration or hypertension. The neural circuits that control hunger and thirst have been well studied but overlapping neural pathways in the control of hunger or of thirst, and the strong interdependence of feeding and drinking has made it difficult to untangle the respective circuits. To address this long-standing problem, this project takes a novel approach that uses the Brattleboro rat to tease apart aspects of the glucagon-like peptide-1 (GLP-1) system that control feeding and drinking. The Brattleboro rat is a well-studied rodent model of central diabetes insipidus that originated in a colony of Long Evans rats. A naturally occurring single nucleotide mutation in these rats results in a vasopressin precursor that cannot be secreted, causing severe polyuria. To compensate for the polyuria, Brattleboro rats drink approximately five times that consumed by wild-type littermates, without any observed feeding-related phenotype. A series of studies in our laboratory suggest that at least part of the polydipsia involves disrupted satiety signals. Specifically, licking microstructure analyses revealed differences that are consistent with altered satiation and additional studies suggest that Brattleboro rats have altered fluid intake-relevant GLP-1 signaling, but intact feeding-related GLP-1 responses. Moreover, Brattleboro rats appear to have different GLP-1 precursor expression in the hindbrain when compared with that of wild type littermates. Taking advantage of these differences in fluid intake, in the absence of differences in food intake, this project uses a variety of approaches to better elucidate circuits responsible for the control of drinking, especially relevant for satiation of thirst, and to separate these from circuits responsible for food intake. Accordingly, by testing for differences between wild-type and Brattleboro rats, we can identify circuits and populations of cells in the GLP-1 system that control drinking and separate them from those that control other functions such as feeding. As such, these data will lead to a more complete understanding of the circuits that control fluid and food intake satiety and provide targets for treatments of disordered energy and fluid homeostasis.

项目摘要：进食和饮水是维持机体能量和营养的基本行为