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: 7895494
• 负责人: Julie S Pendergast
• 金额: $ 5.05万
• 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/7895494
• 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）：主要的哺乳动物起搏器位于下丘脑的视交叉上核（SCN），驱动与环境同步的生理和行为昼夜节律。在温带气候下，动物利用每年日长或光周期的变化来随着季节的变化调整其生理状态。时钟编码光周期的方式尚不清楚，但两个耦合振荡器，一个与早晨 (M) 同步，另一个与晚上 (E) 同步，其相位关系随白天长度而变化，这使得 SCN 能够计算光周期的季节性变化。 这些双振荡器可能嵌入在参与 SCN 内源性昼夜节律生成的分子转录和翻译反馈环中 (4)。时钟基因Period 1 (Perl)是节奏生成的重要组成部分，也参与时钟与光的同步。目前的提案将研究分离的 SCN 在编码光周期 Perl 报告大鼠中的作用，该大鼠是通过将光周期 Fischer 344 (F344) 品系与在 Perl 启动子控制下表达荧光素酶的转基因 Per1::荧光素酶 (Per1::luc) 大鼠杂交而产生的。通过对暴露于短日照或长日照的光周期大鼠的 SCN 分区中的实时 Perl 启动子活性进行成像，可以研究假定的 M 和 E 振荡器的解剖位置。单细胞发光成像将用于检查单个 SCN 神经元内 Perl 启动子活性的光周期依赖性差异。该提案还将通过比较暴露于抑制或允许繁殖日长的大鼠的 Perl 启动子活性谱，研究分子钟在编码允许繁殖的关键光周期中的作用。此外，将确定光周期 F344 和非光周期 Wistar 大鼠的 SCN 中的光周期编码是否不同。光周期的季节变化也可能影响人类的神经过程。公共卫生相关性 许多被诊断患有季节性情感障碍 (SAD) 的患者仅在秋季和冬季经历抑郁发作，清晨强光治疗可以纠正其昼夜节律的延迟。因此，研究 SCN 在编码光周期中的作用可能会为 SAD 患者开发新的治疗方法。