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SLEEP/WAKE RHYTHMS IN AGING--TREATMENT WITH NIMODIPINE

衰老过程中的睡眠/觉醒节律——尼莫地平治疗

基本信息

批准号：
6488816
负责人：
SUSAN J BENLOUCIF
金额：
$ 10.92万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-01-01 至 2002-12-31
项目状态：
已结题

项目摘要

The purpose of this project is to gain a basic understanding of the causes of chronic sleep disturbances in older adults and to develop effective therapies for these problems. Altering the age-related changes in the endogenous circadian pacemaker and reducing exposure to bright light can improve the sleep performance in elderly persons. However, age-related changes in synaptic plasticity arising from impaired calcium regulation may decrease the responsiveness of the aging clock to light. Recent findings indicate that treatment with the L-type calcium channel antagonist, nimodipine, can improve light-induced phase shifts of circadian activity rhythms in old mice. This indicates that nimodipine may also improve the response of the clock to light. The goals of this project are to test the hypothesis that responsiveness to light is decreased in the clock of older humans, and that enhancing the responsiveness of the clock to light with nimodipine will normalize disrupted sleep/wake rhythms in an animal model of aging. The specific aims of the project are to 1) assess the conditions under which nimodipine reverse age-related deficits in responsiveness of the clock to light in mice by testing the effects of different treatment regimens on three measures of circadian responsiveness to light in young, middle aged, and old mice; 2) test the hypothesis that nimodipine will restore normal entrainment patterns to a light/dark cycle in aged C3H/HeN mice by measuring the amplitude of the diurnal activity rhythm and the phase angle of entrainment; 3) test the hypothesis that older humans exhibit a decrease in the responsiveness of the clock to light by assessing the light-induced suppression of nocturnal melatonin levels and phase shifts of circadian rhythms in young and old subjects; and 4) determine the light intensity required to improve sleep and daytime performance in elderly subjects by assessing the effect of daily administration of three different intensities of light on neuropsychological performance and sleep in older adults. The results of the animal and human experiments are designed to determine if nimodipine can enhance the effectiveness of light therapy for sleep/wake disorders in elderly humans.

该项目的目的是对原因有一个基本的了解老年人慢性睡眠障碍的研究并制定有效的针对这些问题的疗法。改变与年龄相关的变化内源性昼夜节律起搏器和减少暴露在强光下可以改善老年人的睡眠表现。但与年龄有关钙调节受损引起的突触可塑性变化可能会降低老化时钟对光的响应能力。最近的研究结果表明，用 L 型钙通道治疗拮抗剂尼莫地平可以改善光诱导的相移年老小鼠的昼夜节律活动。这表明尼莫地平可能还可以提高时钟对光的响应。该项目的目标是为了检验以下假设：对光的反应能力在老年人的时钟，并提高了反应能力使用尼莫地平进行时钟调整将使紊乱的睡眠/觉醒节律正常化在衰老动物模型中。该项目的具体目标是 1) 评估尼莫地平逆转年龄相关缺陷的条件通过测试小鼠时钟对光的反应不同治疗方案对昼夜节律反应性的三种测量对年轻、中年和老年小鼠进行照明； 2）检验假设尼莫地平将恢复正常的光/暗循环夹带模式通过测量老年 C3H/HeN 小鼠的昼夜活动幅度节奏和夹带的相位角； 3）检验假设老年人的生物钟反应能力下降光通过评估光诱导的夜间褪黑激素抑制年轻和年长受试者的昼夜节律水平和相移； 4) 确定改善睡眠和白天所需的光强度通过评估每天的效果来评估老年受试者的表现三种不同强度的光的管理老年人的神经心理学表现和睡眠。结果动物和人体实验旨在确定尼莫地平是否可以增强光疗法对睡眠/觉醒障碍的有效性老年人。