Chronic effects of acute stress

急性应激的慢性影响

基本信息

批准号：
7368079
负责人：
Ruth B Harris
金额：
$ 25.12万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-03-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7368079
关键词：
Acute Adrenal Cortex Animals Anxiety Behavior Behavioral Body Weight Body Weight decreased Brain Brain Stem Cell Nucleus Chronic Classification Condition Corticosterone Corticotropin-Releasing Hormone Corticotropin-Releasing Hormone Receptors Data Depth Development Dexamethasone Diet Down-Regulation Eating Endocrine Energy Metabolism Environment Equilibrium Exhibits Exposure to Fat-Restricted Diet Fatty acid glycerol esters Feedback Figs - dietary Financial compensation Food Future Glucocorticoids Homeostasis Hormones Hour Housing Hypersensitivity Hypothalamic structure Individual Infusion procedures Injection of therapeutic agent Intervention Investigation Lead Leptin Ligands Maintenance Measures Medial Dorsal Nucleus Messenger RNA Modeling Mus Norepinephrine Nucleus solitarius Numbers Obesity Overweight Pathway interactions Peptides Peripheral Phenotype Physiology Rate Rattus Recovery Regulation Research Personnel Role Saline Serum Site Stream Stress Structure of area postrema Structure of nucleus infundibularis hypothalami Sympathetic Nervous System System Testing Tube Water Weight Weight Gain acute stress antisauvagine 30 base biological adaptation to stress day energy balance feeding food restriction interest lateral ventricle neural circuit neurochemistry novel novel strategies paraventricular nucleus prevent programs receptor relating to nervous system research study response restraint restraint stress stressor urocortin II

项目摘要

DESCRIPTION (provided by applicant): Studies in this proposal investigate the chronic effects of acute stress on long-term regulation of body weight. Rats exposed to 3 hours of restraint on each of 3 consecutive days lose weight on the days of stress and gain weight when stress ends, but do not return to the weight of their non-stressed controls. Thus, repeated restraint provides a unique model in which acute stress results in a chronic reduction in body weight. Identification of mechanisms responsible for this sustained reduction in body weight will provide new information on the normal regulation of body weight and may lead to novel strategies for successful maintenance of weight loss in overweight individuals. Although we have determined that initiation of weight loss is dependent upon activation of central corticotropin releasing factor Type 2 (CRF2) receptors adjacent to the 3rd and/or 4th ventricle, we have not identified sustained changes in the basal neurochemical or endocrine status of the animals during the post-stress period. We have, however, shown that feeding rats a high-fat (40 percent kcal fat) diet exaggerates the response to stress by inducing a greater weight loss and have observed that rats that have been exposed to repeated restraint stress show an exaggerated endocrine and hypophagic response to a subsequent mild stress. We hypothesize that acute stress causes a chronic hyper-reactivity of aspects of the CRF system that are both stress-responsive and are involved in the regulation of energy homeostasis. Hyper-reactivity of the CRF system may prevent recovery of body weight in stressed rats. The sensitivity of these same systems also is influenced by diet composition to increase stress responsiveness in rats fed a high-fat diet. Specific Aim 1 will test whether rats that have been exposed to repeated restraint stress exhibit an exaggerated neurochemical, energetic and behavioral response to a subsequent mild stress, which would be indicative of an increased reactivity of the CRF system. Specific Aim 2 will test whether feeding a high-fat diet results in a hyper-responsiveness of the CRF system or a suppression of the post-stress down-regulation of CRF activity, to clarify whether increased stress responsiveness is caused by the same mechanisms in high-fat fed rats as in rats that have been exposed to repeated restraint. Specific Aim 3 will identify nuclei in the hypothalamus and brainstem that are critical for stress-induced weight loss.

描述（由申请人提供）：该提案中的研究研究了急性应激对体重长期调节的慢性影响。接触3小时约束的大鼠连续3天会在压力时减轻体重，并在压力结束时体重增加，但不会恢复其无压力控制的重量。因此，重复的约束提供了一个独特的模型，其中急性应力会导致体重长期减轻。识别负责这种持续减轻体重的机制将提供有关正常体重调节的新信息，并可能导致成功维持超重个人体重减轻的新策略。尽管我们已经确定体重减轻的开始取决于中央皮质激素释放因子2型（CRF2）受体的激活与第3和/或4个心室相邻，但我们尚未确定在折伤后动物的基础神经化学或内分泌状态的持续变化。但是，我们已经表明，喂养大鼠高脂（40％kcal脂肪）饮食可以通过诱发更大的体重减轻来夸大对压力的反应，并观察到已经暴露于重复的约束应力的大鼠表明内分泌和下分泌反应对随后的轻度压力。我们假设急性应激会导致CRF系统各个方面的慢性高反应性，这既具有应力响应性，又参与了能量稳态的调节。 CRF系统的过度反应性可以防止压力大鼠体重恢复。这些相同系统的敏感性也受饮食组成的影响，以增加喂养高脂饮食的大鼠压力反应性。具体目标1将测试暴露于重复约束应力的大鼠是否表现出对随后的轻度压力的夸张的神经化学，能量和行为反应，这表明CRF系统的反应性增加。具体目标2将测试喂养高脂饮食是否会导致CRF系统的过度反应性或抑制CRF活性后压力下调的抑制，以阐明增加的压力反应性是否是由高脂喂养大鼠在暴露于重复约束的大鼠中的相同机制引起的。特定的目标3将识别下丘脑和脑干中的核，对于压力引起的体重减轻至关重要。