The role of the circadian clock in encoding seasonal variations in day length

生物钟在编码日长季节变化中的作用

• 批准号: 7673609
• 负责人: Julie S Pendergast
• 金额: $ 4.72万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7673609
• 关键词: Affect; Animal Model; Animals; Anterior Hypothalamus; Argipressin; Behavior; Biological Rhythm; Biology; Biomedical Research; Biometry; Brain; Cells; Circadian Rhythms; Climate; Communities; Coupled; Data; Detection; Development; Diagnosis; Educational workshop; Environment; Feedback; Future; Generations; Genes; Goals; Hamsters; Human; Hypothalamic structure; Image; In Vitro; Individual; Journals; Laboratory mice; Lead; Life; Light; Location; Luciferases; Mammals; Measures; Molecular; Molecular Biology; Molecular Profiling; Mus; Neurologic; Neurons; Neurosciences; Pacemakers; Patients; Phase; Photons; Photoperiod; Physiological; Physiology; Population; Process; Rattus; Reporter; Reproduction; Research; Research Personnel; Resolution; Role; Seasonal Affective Disorder; Seasonal Variations; Seasons; Slice; Societies; System; Techniques; Testing; Time; Training; Transgenic Organisms; Universities; Wistar Rats; Work; career; career development; cellular imaging; circadian pacemaker; day length; depressive symptoms; experience; falls; horizontal cell; in vivo; luminescence; meetings; novel; novel therapeutics; promoter; public health relevance; research study; suprachiasmatic nucleus

DESCRIPTION (provided by applicant): The primary mammalian pacemaker, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, drives circadian rhythms in physiology and behavior that are synchronized with the environment. In temperate climates, animals use annual changes in day length, or photoperiod, to adjust their physiological state with changes in season. The way in which the clock encodes photoperiod is unknown, but two coupled oscillators, one synchronized to morning (M) and the other synchronized to evening (E), whose phase relationship varies with day length would allow the SCN to compute seasonal changes in photoperiod. These dual oscillators may be embedded in the molecular transcriptional and translational feedback loops that participate in endogenous circadian rhythm generation in the SCN (4). The clock gene, Period 1 (Perl), is an important component of rhythm generation and also participates in the synchronization of the clock to light. The current proposal will investigate role of the isolated SCN in encoding day length in photoperiodic Perl reporter rats generated by crossing the photoperiodic Fischer 344 (F344) strain with transgenic Per1::luciferase (Per1::luc) rats that express luciferase under the control of the Perl promoter. The anatomical locations of putative M and E oscillators will be investigated by imaging real-time Perl promoter activity in subdivisions of the SCN in photoperiodic rats exposed to either short or long day lengths. Singlecell luminescence imaging will be used to examine photoperiod-dependent differences in Perl promoter activity within an individual SCN neuron. This proposal will also investigate the role of the molecular clock in encoding the critical photoperiod permissive for reproduction by comparing the Perl promoter activity profile of rats exposed to either inhibitory or permissive day lengths for reproduction. Furthermore, it will be determined whether photoperiod encoding in the SCN differs between photoperiodic F344 and nonphotoperiodic Wistar rats. Seasonal variations in photoperiod may also affect neurological processes in humans. PUBLIC HEALTH RELEVANCE Many patients diagnosed with seasonal affective disorder (SAD) experience depressive episodes only during the fall and winter, and treatment with early morning bright light corrects the delay in their circadian rhythms. Therefore, investigating the role of the SCN in encoding photoperiod may lead to the development of novel therapeutic treatments for SAD patients.

描述（由申请人提供）：位于下丘脑视交叉上核（SCN）中的初级哺乳动物起搏器驱动与环境同步的生理和行为的昼夜节律。在温带气候中，动物利用日长或光周期的年度变化来调整其生理状态。时钟编码光周期的方式尚不清楚，但两个耦合振荡器，一个同步到早晨（M），另一个同步到晚上（E），其相位关系随白天的长度而变化，将允许SCN计算光周期的季节变化。 这些双振荡器可能嵌入在参与SCN内源性昼夜节律产生的分子转录和翻译反馈环中（4）。时钟基因，周期1（Perl），是节奏产生的重要组成部分，也参与了时钟与光的同步。目前的建议将调查的作用，分离的SCN在编码的光周期Perl报告大鼠通过交叉的光周期Fischer 344（F344）株与转基因的Per1：：荧光素酶（Per1：：luc）的Perl启动子的控制下表达荧光素酶的大鼠。假定的M和E振荡器的解剖位置将通过成像的实时Perl启动子的活性在SCN的分区中暴露于短或长的日照长度的光周期大鼠进行研究。单细胞发光成像将被用来检查在一个单独的SCN神经元内的Perl启动子活性的光周期依赖性差异。该提案还将调查的分子时钟的作用，在编码的关键光周期允许生殖的Perl启动子活性曲线的大鼠暴露于抑制或允许的一天长度的生殖比较。此外，将确定光周期性F344和非光周期性Wistar大鼠之间SCN中的光周期编码是否不同。光周期的季节性变化也可能影响人类的神经过程。许多被诊断为季节性情感障碍（SAD）的患者只在秋季和冬季经历抑郁发作，清晨明亮的光线治疗可以纠正他们昼夜节律的延迟。因此，研究SCN在编码光周期中的作用可能会导致SAD患者新的治疗方法的开发。