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Sex differences and metabolic responses to chronic stress

性别差异和对慢性压力的代谢反应

基本信息

批准号：
10313851
负责人：
Carley Dearing
金额：
$ 3.79万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10313851
关键词：
Acute Address Angiotensin II Animals Bilateral Blood Glucose Blood Pressure Blood specimen Body Temperature Brain Stem Cannulas Cardiovascular Diseases Cause of Death Chronic Chronic stress Code Corticosterone Corticotropin-Releasing Hormone Data Diabetes Mellitus Disease Doctor of Philosophy Eating Endocrine Environment Epidemic Epidemiology Exposure to Fellowship Female Fiber Optics Future Glucagon Glucocorticoids Glucose Glucose Intolerance Glucose tolerance test Glutamates Goals Health Heart Rate Hormones Hypothalamic structure Immunohistochemistry Impairment Individual Insulin Link Measures Mental Depression Messenger RNA Metabolic Metabolic Diseases Metabolic dysfunction Metabolic hormone Metabolism Neuroendocrinology Pathogenesis Personal Satisfaction Physiological Physiology Positioning Attribute Predisposition Prefrontal Cortex Preparation Process Psychological Stress Quality of life Randomized Rattus Research Research Personnel Role Science Scientist Sex Differences Signal Transduction Societies Stress Synapses Testing Time Training Viral acute stress biological adaptation to stress blood glucose regulation cardiometabolic risk cardiovascular disorder risk career cognitive process disability doctoral student frontal lobe hemodynamics hypothalamic-pituitary-adrenal axis insight knowledge base male mortality neural circuit neuromechanism novel optogenetics programs psychologic psychological stressor relating to nervous system response restraint sex socioeconomics stress reactivity stressor years lived with disability

项目摘要

Project Summary This proposal aims to train a dual-degree, DVM-PhD, student in preparation for a successful career as a clinician-scientist. The applicant will earn a PhD in Biomedical Sciences while simultaneously earning a DVM. Given that cardiovascular disease and metabolic disorders are an increasingly prevalent global epidemic and these disorders significantly contribute to both increased mortality and increased years lived with disability, it is vital to understand the pathogenesis of these disorders. Epidemiologically, chronic stress has a prominent role in cardiometabolic risk. Neural processes are known to influence physiologic responses to stress. However, the specific mechanisms that underlie sex-dependent changes in endocrine and metabolic physiology after chronic stress are not well understood. Therefore, the research outlined in this proposal aims to determine how specific neural circuitry influences stress reactivity and, consequently, metabolic health in male and female rats. Specifically, testing the hypothesis that signaling from the infralimbic cortex (IL) to the rostral ventrolateral medulla (RVLM) mitigates endocrine stress reactivity after chronic stress in a sex-specific manner. The following specific aims will be addressed: 1) determines if activation of the IL-RVLM circuit mitigates endocrine responses to glycemic challenge and psychological stress in male and female rats. 2) Determines if activation of the IL-RVLM circuit following exposure to chronic stress reduces female susceptibility to endocrine hyper- reactivity. Activation of the IL-RVLM circuit will be achieved using optogenetic stimulation. Acute restraint will be used as a psychological stressor to measure activation of stress hormones, namely glucocorticoids, glucose, glucagon, angiotensin II, and insulin. Glycemic challenge in the form of a glucose tolerance test will be used a metabolic stressor. In aim 2, chronic variable stress (CVS) exposure will consist of 14 days of twice- daily randomized stressors. Following exposure to CVS, animals will undergo acute restraint and glycemic challenge. In addition to stress hormones, glucose, glucagon, angiotensin II and insulin, non-invasive measures of metabolism and autonomic activation such as heart rate, blood pressure, and body temperature will be taken during acute stress in both aims. Corticotropin Releasing Hormone mRNA will be quantified in the hypothalamus. Additionally, basal metabolic measures will be taken in the form of bodyweight and food intake. Taken together, these studies will provide novel insight into how cortical and brainstem processes integrate to influence metabolic health in a sex-specific manner. This will further our understanding of how stress contributes to metabolic and cardiovascular diseases.

项目总结