SLEEP AND METABOLIC CONSEQUENCES OF CHRONIC PARTIAL SLEEP RESTRICTION IN RATS

大鼠慢性部分睡眠限制的睡眠和代谢后果

• 批准号: 8245079
• 负责人: FRED W TUREK
• 金额: $ 24.08万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8245079
• 关键词: Adipose tissue; Adverse effects; Affect; Age; Age-Months; Aging; Animal Model; Animals; Appetite Depressants; Architecture; Area; Autopsy; Awareness; Behavioral; Biological; Blood specimen; Body mass index; Brain; Cardiovascular Diseases; Cholesterol; Chronic; Circadian Rhythms; Clinical Research; Corticosterone; Data; Development; Diabetes Mellitus; Disease; Doctor of Philosophy; Dose; Elderly; Electroencephalography; Energy Metabolism; Environment; Epidemiologic Studies; Equilibrium; Exhibits; Experimental Animal Model; Fatigue; Frequencies; Funding; Gene Expression; Gene Expression Regulation; Genes; Genetic; Glucocorticoids; Glucose; Glucose tolerance test; Health; Homeostasis; Hormonal; Human; Hypothalamic structure; Inflammatory; Instruction; Insulin; Intervention; Investigation; Lead; Leptin; Life; Link; Liver; Long-Term Effects; Metabolic; Metabolism; Modeling; Molecular; Monitor; Neurosecretory Systems; Nonesterified Fatty Acids; Obesity; Pattern; Peripheral; Phenotype; Physiological; Physiological Processes; Principal Investigator; Procedures; Protocols documentation; REM Sleep; Rattus; Recovery; Regulation; Risk; Rodent; Severities; Signal Transduction; Sleep; Sleep Architecture; Sleep disturbances; Societies; System; Testing; Time; Tissues; Transcript; Triglycerides; Work; age effect; age related; alertness; allostasis; allostatic load; carbohydrate metabolism; circadian pacemaker; coping; cytokine; ghrelin; glucose tolerance; indexing; insight; juvenile animal; lipid metabolism; male; metabolic abnormality assessment; middle age; new technology; novel; novel therapeutics; programs; research study; response; sex; sleep regulation; trait

Seeinstructions): Chronic partial sleep restriction (CPSR) is a hallmark of life in modern human society however, only recently have the consequences of CPSR for chronic human illnesses such as obesity and diabetes come to be fully appreciated. Despite the growing awareness of the importance of sleep as a factor in human health and in the development of age-related diseases, few animal models have been developed to systematically determine how aging effects the consequences of CPSR on the sleep-wake regulatory system itself and on other physiological processes, such as energy metabolism and circadian rhythms. During the previous funding period, we developed a model of CPSR that led to the exciting discovery that after only a few days of CPSR, both young and old rats no longer exhibited a homeostatically regulated sleep recovery pattern; they failed to generate increases in NREM EEG delta power and NREM sleep time. In addition, we demonstrated an impact of CPSR on leptin and glucocorticoid concentrations, glucose tolerance, and insulin responsiveness in young rats. These data led us postulate a novel hypothesis that repeated episodes of sleep restriction result in the transition from a homeostatic to an allostatic state of sleep regulation that may lead to adaptive changes in the sleep-wake and other physiological systems to cope with the immediate environmental challenge inducing sleep loss. However, such initially adative changes could have adverse effects if the allostatic response to CPSR is maintained for a prolonged period of time. In the proposed studies, we will systematically examine this working model in two Specific Aims (1) Test the hypothesis that aging accelerates the transition from homeostatis to allostasis during CPSR. Specifically, we will determine if aging impacts the severity and duration of sleep restriction necessary to cause the transition from a homeostatic to an allostatic sleep regulatory state (2) Test the hypothesis that aging alters the effects of CPSR on key hormonal and molecular components of energy metabolism and circadian clock gene expression in the CMS and peripheral tissues, and that the adverse effects of CPSR on metabolism are a consequence and are exacerbated by the transition from a homeostatic to an allostatic sleep regulatory state RELEVANCE (See instructions): The use of an animal model to determine the effects of chronic partial sleep restriction (CPSR) and how aging impacts the response to CPSR, is expected to lead to new insights into the biological mechanisms that link short sleep in humans with cardiometabolic diseases, and new therapeutic strategies for treating age- related metabolic and associated disorders, such as obesity, diabetes, and cardiovascular disease.

see Instructions）： 慢性部分睡眠限制（CPSR）是现代人类社会生活的标志 有CPSR对肥胖和糖尿病等慢性人类疾病的后果 感谢。尽管人们对睡眠的重要性越来越认识，这是人类健康和中的一个因素 与年龄相关疾病的发展，很少有动物模型被系统地开发 确定衰老如何影响CPSR对睡眠效果调节系统本身以及对 其他生理过程，例如能量代谢和昼夜节律。在上一个 资金期，我们开发了一种CPSR模型，导致令人兴奋的发现，仅几天后 CPSR的年轻大鼠和老鼠不再表现出体内稳态调节的睡眠恢复模式。他们 无法产生NREM EEG DELTA功率和NREM睡眠时间的增加。此外，我们证明了 CPSR对瘦素和糖皮质激素浓度，葡萄糖耐受性和胰岛素的影响 年轻大鼠的响应能力。这些数据导致我们假设一个新的假设，该假设重复了 睡眠限制导致从体内平衡到同性睡眠状态的过渡可能 导致睡眠觉醒和其他生理系统的自适应变化，以应对即时 环境挑战引起睡眠损失。但是，这种最初的善良变化可能会有不利的 如果长时间维持对CPSR的同性反应，则影响。在提议中 研究，我们将在两个具体目标中系统地检查该工作模型（1）检验以下假设。 在CPSR期间，衰老加速了从稳态向Allostasis的过渡。具体来说，我们将确定是否 衰老会影响导致从A的过渡所必需的睡眠限制的严重性和持续时间 稳态到同性睡眠调节状态（2）检验了衰老的假设，即老化会改变 CPSR在能量代谢的关键激素和分子成分和昼夜节律基因的基因上 在CMS和外围组织中的表达，CPSR对代谢的不利影响是A 从体内稳态到同性睡眠调节状态的过渡会加剧并加剧 相关性（请参阅说明）： 使用动物模型来确定慢性部分睡眠限制（CPSR）的影响以及如何 衰老会影响对CPSR的反应，预计将导致对生物学机制的新见解 将人类短睡眠与心脏代谢疾病联系起来，以及治疗年龄的新治疗策略 - 相关的代谢和相关疾病，例如肥胖，糖尿病和心血管疾病。