Oxidative Stress Responses to Loss and Recovery of Sleep

氧化应激对睡眠不足和恢复的反应

• 批准号: 7629148
• 负责人: CAROL A EVERSON
• 金额: $ 31.5万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7629148
• 关键词: Address; Adverse effects; Affect; Animal Model; Animals; Antioxidants; Apoptosis; Apoptotic; Biochemical; Biochemical Process; Biological; Biological Markers; Biology; Body Weight decreased; Cell Death; Cell Proliferation; Cell physiology; Cells; Cellular Stress; Cessation of life; Clinical; Clinical Pathology; DNA; DNA Damage; DNA Fragmentation; Data; Development; Diagnostic; Disease; Drug Formulations; Employee Strikes; Enzymes; Equilibrium; Event; Financial compensation; Free Radicals; Functional disorder; Future; Goals; Healed; Heart; Hepatic Tissue; Homeostasis; Hormones; Hyperphagia; Immune; Immunoassay; Impaired health; Injury; Intervention; Investigation; Laboratories; Laboratory Animals; Lipids; Liver; Location; Mediating; Mediation; Mediator of activation protein; Medical; Medicine; Metabolic; Methods; Morbidity - disease rate; Nature; Organ; Outcome; Oxidative Stress; Peripheral; Physiological; Physiological Processes; Physiology; Positioning Attribute; Process; Property; Proteins; Rattus; Recovery; Research; Research Design; Research Personnel; Risk Factors; Series; Serum Markers; Site; Sleep; Sleep Deprivation; System; Testing; Tissues; Work; base; biological adaptation to stress; body system; cell injury; cellular targeting; clinically significant; disorder prevention; healing; interdisciplinary approach; light microscopy; microorganism; prevent; programs; repaired; research study; response; restoration

DESCRIPTION (provided by applicant): Widely accepted are two notions: sleep deprivation impairs health and sleep recovery has dynamic healing powers. The rationale for the proposed research is that specific tissues have not yet been identified as being in need of repair after sleep deprivation or "restored" by sleep recovery. Our long-term goal is to provide tangible evidence of physiological processes and outcomes that compose the properties of sleep and sleep loss. Sleep deprivation in the animal model produces a condition that eventually becomes highly lethal, lacks specific localization, and is reversible with sleep, implying mediation by a biochemical process or functional abnormality. Recent findings in sleep-deprived rats have provided evidence that the missing biological mediation is oxidative stress and antioxidant depletion. The objectives of this proposal are to identify targets of oxidative stress-associated damage and to determine the extent to which antioxidant depletion and cell damage affect physiological and clinical signs. The central hypothesis is that reductions in antioxidant status cause widespread increases in repairable and irreparable cell damage within multiple regulatory systems, leading ultimately to inadequate compensation and to the development of pathophysiological signs. Preliminary data support the formulation of this hypothesis by providing evidence of increased DNA damage and apoptosis in hepatic tissue undergoing oxidative stress induced by sleep loss. Antioxidant enzymes fail to respond in compensation until sleep is again permitted. In experiments under Aim 1, damage to cellular lipid, protein, and DNA targets of oxidative stress and localization of damage to specific organ-systems will be determined in rats during sleep loss and recovery. Experiments under Aim 2 will determine the extent of cell injury leading to cell death and to increased cell repair and renewal during sleep loss and recovery. Studies under Aim 3 will test the extent to which manipulation of antioxidant status can change sleep deprivation-induced cell damage and physiological signs. The proposed research is collaborative and integrates expertise in sleep physiology and free radical biology. The research design is composed of planned comparisons of different durations of sleep deprivation, sleep restriction, and control conditions. Analyses include biochemical, immunoassay, and immunohistochemical methods. The significance of the proposed research is advancement of medical interventions that promote the restorative functions of sleep.

描述（由申请人提供）：被广泛接受的是两个概念：睡眠剥夺损害健康和睡眠恢复具有动态的治愈能力。拟议的研究的理由是，尚未确定特定的组织在睡眠剥夺后需要修复或通过睡眠恢复“恢复”。我们的长期目标是提供构成睡眠和睡眠损失特性的生理过程和结果的切实证据。动物模型中的睡眠剥夺会产生一种最终变得高度致命的状况，缺乏特定的定位，并且在睡眠中可逆，这意味着通过生化过程或功能异常进行调解。在睡眠不足的大鼠中的最新发现提供了证据，表明缺失的生物学介导为氧化应激和抗氧化剂耗竭。该提案的目标是确定氧化应激相关损伤的靶标，并确定抗氧化剂耗竭和细胞损伤影响生理和临床体征的程度。中心假设是，抗氧化剂状态的降低会导致多个调节系统内可修复和无法弥补的细胞损伤的广泛增加，最终导致补偿不足和病理生理体征的发展。初步数据通过提供增加的DNA损伤和细胞凋亡的证据来支持该假设的制定，并在经历睡眠损失引起的氧化应激的肝组织中。抗氧化剂酶无法以补偿作出反应，直到再次允许睡眠为止。在AIM 1下的实验中，在睡眠丧失和恢复过程中，将确定对大鼠的细胞脂质，蛋白质和DNA靶标的损害以及对特定器官系统损伤的定位。 AIM 2下的实验将确定导致细胞死亡的细胞损伤程度，并在睡眠丧失和恢复过程中增加细胞修复和更新。 AIM 3下的研究将测试抗氧化剂状态的操纵可以改变睡眠剥夺引起的细胞损伤和生理体征的程度。拟议的研究是协作性的，并整合了睡眠生理学和自由基生物学方面的专业知识。研究设计由计划的睡眠剥夺，睡眠限制和控制条件的计划比较组成。分析包括生化，免疫测定和免疫组织化学方法。拟议研究的重要性是医疗干预措施的进步，这些干预措施促进了睡眠的恢复功能。