Sleep and fatigue during renal disease in mice

描述（由申请人提供）：嗜睡和睡眠质量广泛影响一般健康状况的测量，特别是影响对能量，疲劳和一般健康的看法。疲劳和睡眠紊乱也是患有慢性疾病或接受相关治疗的人的常见致残问题。特别是，患有肾脏疾病的人经常出现睡眠紊乱和严重疲劳，这些症状可以独立于透析而发生。有趣的数据支持睡眠、免疫功能和感染性或炎症性疾病之间的重要相互作用，但在这些疾病中疲劳和睡眠紊乱的原因尚不确定。确定在疾病状态下调节睡眠和警惕性的物质和机制，应有助于最终开发出能够控制或预防这些使人衰弱的症状的干预措施，从而改善许多人的生活质量。

DESCRIPTION (provided by applicant): Sleepiness and sleep quality broadly influence measures of general health status, particularly impacting perceptions about energy, fatigue, and general well being. Fatigue and disturbed sleep are also common and disabling problems for persons undergoing chronic diseases or associated therapies. In particular, people with renal disease frequently develop disturbed sleep and severe fatigue that can occur independent of dialysis. Intriguing data support significant interactions between sleep, immune function, and infectious or inflammatory disease, but the cause of fatigue and disturbed sleep during such disorders is uncertain. Identifying substances and mechanisms that modulate sleep and vigilance during disease states should contribute to the eventual development of interventions that can control or prevent these debilitating symptoms and thus improve the quality of life of many people. Our preliminary data indicate that inbred mice undergoing acute pyelonephritis induced by Candida albicans develop strain-dependent variation in patterns of sleep, and varying severity of disease. Our working model is that variation in the host defense response is linked to the development of symptoms such as fatigue and disturbed sleep, and to disease susceptibility and severity. Our long-term goal is to define this complex pathophysiologic network. Toward that end, we propose a genome-wide search to identify a still unknown set of genes that contribute to variation in the behavioral and/or physiologic responses to infection-induced renal disease. These studies will provide critical data necessary to definitively identify the genes that mediate alterations in sleep and to link those genes to other markers of illness. Aim 1 will assess murine strain differences in sleep during toxic nephropathy. Aims 2 and 3 will scan the genome to locate regulatory "hot spots." Aim 4 will capitalize on those findings by assessing the contribution of strong candidate genes. Achieving this ambitious goal is feasible given the experience of my laboratory in surveying sleep phenotypes in other studies involving large numbers of mice.