Potentiation of photic circadian clock phase shifts

光生物钟相移的增强

基本信息

批准号：
7454623
负责人：
MARY E HARRINGTON
金额：
$ 0.93万
依托单位：
SMITH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-05-01 至 2008-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Arousal and sleep deprivation can regulate circadian rhythms in multiple ways. One extremely important effect is the ability of these non-photic, higher level inputs to antagonize the synchronizing effects of light, as shown, for example, in studies where non-photic stimuli can block photic phase shift responses. We recently discovered that blocking the non-photic neuropeptide Y (NPY) input pathway to the suprachiasmatic nuclei (SCN) can potentiate photic phase shifting, suggesting that this pathway tonically suppresses the effects of light, and pharmacological treatments can release the animal from these inhibitory effects. We know that non-photic inputs to the circadian clock are represented by both NPY and serotonergic pathways. Remarkably, blocking both NPY and serotonergic inputs potentiates photic effects to an even greater degree, such that a 5 min light pulse is able to induce a 7 h phase shift of circadian rhythms of a treated hamster, as compared to a circa-1 h phase shift in an untreated hamster. This grant will build upon these findings of greatly potentiated light-induced phase shifts when the arousal-related NPY and serotonergic inputs are pharmacologically blocked. We will test these hypotheses: Hypothesis 1: NPY Y5 and serotonin 5HT1A receptors regulate the phase shifting effects of light at multiple phases throughout the subjective night. Hypothesis 2: Non-input inputs do not need to coincide with light, but can alter the response to light when presented within 1 h of light onset or offset. Hypothesis 3: NPY and 5HT inputs alter light-induction of per1 and per2 gene expression. The capability of NPY and serotonin antagonists to potentiate and agonists to attenuate the effects of light on the circadian system could be a potentially useful tool in clinical research. In cases of entrainment disorders, such as delayed or advanced sleep phase syndrome, potentiating the effects of light at one time while blocking effects of light at another phase might be an approach to correct the phase of entrainment. Symptoms of jet lag might be shortened in duration if resetting effects of light in the new time zone are potentiated. Shift workers might benefit from blocking the effects of light at night. The progress of cancer is slower in patients with enhanced circadian rhythmicity, a benefit that might accrue from better circadian entrainment

描述（由申请人提供）：觉醒和睡眠剥夺可以通过多种方式调节昼夜节律。一个极其重要的效应是这些非光的、更高水平的输入对抗光的同步效应的能力，例如，在非光刺激可以阻止光相移响应的研究中所示。我们最近发现，阻断到视交叉上核（SCN）的非光神经肽Y（NPY）输入途径可以增强光相移，这表明该途径可以强性抑制光的影响，而药物治疗可以将动物从这些抑制中释放出来。影响。我们知道生物钟的非光输入由 NPY 和血清素通路代表。值得注意的是，阻断 NPY 和血清素输入会更大程度地增强光效应，因此与大约 1 小时的相位相比，5 分钟的光脉冲能够诱导治疗仓鼠的昼夜节律发生 7 小时的相位变化未经治疗的仓鼠发生转变。这项资助将建立在当唤醒相关的 NPY 和血清素输入被药理学阻断时大大增强的光诱导相移的这些发现的基础上。我们将测试这些假设：假设 1：NPY Y5 和血清素 5HT1A 受体在整个主观夜晚的多个阶段调节光的相移效应。假设 2：非输入输入不需要与光一致，但在光开始或偏移后 1 小时内出现时可以改变对光的响应。假设 3：NPY 和 5HT 输入改变 per1 和 per2 基因表达的光诱导。 NPY 和血清素拮抗剂增强光对昼夜节律系统影响的能力以及激动剂减弱光对昼夜节律系统影响的能力可能是临床研究中潜在有用的工具。在夹带障碍的情况下，例如睡眠相位延迟或提前综合征，在某个时间增强光的影响，同时阻止另一阶段的光的影响可能是纠正夹带相位的一种方法。如果新时区的光线重置效果得到加强，时差症状的持续时间可能会缩短。轮班工人可能会受益于阻挡夜间光线的影响。昼夜节律增强的患者癌症进展较慢，更好的昼夜节律可能会带来好处