SLEEP/WAKE RHYTHMS IN AGING--TREATMENT WITH NIMODIPINE

这个项目的目的是对原因有一个基本的了解。 治疗老年人的慢性睡眠障碍，并开发出有效的 这些问题的治疗方法。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 改善老年人的睡眠状况。然而，与年龄相关的 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性。近期 研究结果表明，运用L型钙离子通道治疗 拮抗剂尼莫地平可以改善光诱导的细胞相移。 老年小鼠的昼夜活动节律。这表明尼莫地平可能 还可以提高时钟对光的反应。这个项目的目标是 是为了验证这样一个假设，即对光的反应性在 老年人的时钟，并增强了老年人的反应能力 尼莫地平光时钟将使被打乱的睡眠/醒来节律正常化 在衰老的动物模型中。该项目的具体目标是：1) 评估尼莫地平逆转年龄相关性缺陷的条件 在小鼠的时钟对光的反应中，通过测试 不同治疗方案对三种昼夜反应性指标的影响 对幼年、中年和老年小鼠进行照明；2)检验假设 尼莫地平将使正常的夹带模式恢复到光明/黑暗周期 测定老年C3H/HEN小鼠的昼夜活动幅度 旋律和夹带的相角；3)检验假设 上了年纪的人表现出时钟对 通过评估光诱导的夜间褪黑素抑制的光 青年和老年人昼夜节律的水平和相移； 以及4)确定改善睡眠和白天所需的光照强度 老年受试者日常训练效果评估的研究 用三种不同强度的光照射 老年人的神经心理表现和睡眠。结果是 动物和人体实验旨在确定尼莫地平 可以增强光疗法对睡眠/觉醒障碍的有效性 年迈的人类。

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.