CNS MELATONIN TARGETS AND PHOTOPERIOD-INDUCED OBESITY

中枢神经系统褪黑激素目标和光周期诱发的肥胖

• 批准号: 3070210
• 负责人: Timothy Jon Bartness
• 金额: $ 6.18万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3070210
• 关键词: autoradiography; brain mapping; central nervous system; chemical binding; circadian rhythms; environment; fat body; fertility; hamsters; hormone regulation /control mechanism; immunocytochemistry; melatonin; neural transmission; neurotoxins; nutrient intake activity; nutrition related tag; obesity; photobiology; psychosurgery; radiotracer

This grant proposal is a request for an ADAMHA RSDA (Level II). Humans and other animals display seasonal changes in body weight. The environmental signal for this response and for seasonal reproduction cycles in some species is daylength change, the neuroendocrine transducer of which is the pineal gland and its hormone, melatonin (MEL). Furthermore, the duration is the critical feature of the nocturnal MEL secretion profile. Siberian hamsters will be studied, a species that exhibit dramatic seasonal fluctuations in body fat following exposure to short 'winter-like' photoperiods. The goal of this research is to identify the CNS target sites of MEL that trigger seasonal changes in body fat. The target sites of MEL will be identified by determining: 1) the localization of MEL binding in brain using autoradiography and examining environmental and hormonal influences on MEL binding (e.g., time-of-day, photoperiod, pinealectomy [PINX]), 2) whether lesions of MEL binding sites will eliminate short day-induced changes in body weight and fat, food intake and reproductive status, 3) whether lesions of MEL binding sites block short day responses by eliminating the reception of the short day MEL signal by giving PINX hamsters bearing lesions programmed subcutaneous (s.c.) MEL infusions that mimic the MEL signal associated with transfer to short days, 4) the neural input and output pathways of the target sites using new, highly sensitive anterograde and retrograde tracers, 5) whether short day responses elicited by programmed s.c. MEL infusions can be blocked by selective damage of fibers of passage or cell bodies with microknife cuts and neurotoxins, respectively, in PINX hamsters, 6) whether short day responses can be elicited by directly microinfusing MEL into the target sites in PINX hamsters, and 7) the neurochemical substrate that receives the MEL signal by immunocytochemical methods. These studies should identify the CNS site(s) responsible for the photoperiodic (MEL) control of several seasonal cycles and add to our understanding of how naturally-occurring changes in the environment can have dramatic effects on body fat. The acquisition of the neuroanatomical techniques will compliment the interdisciplinary research program of the Principal Investigator and create a unique research environment for examining brain/behavior/energy metabolism.

该赠款提案是对Adamha RSDA（II级）的要求。人类和 其他动物显示体重的季节性变化。环境 此反应的信号和某些季节性繁殖周期的信号 物种是日长度变化，神经内分泌传感器的变化是 松果体及其激素，褪黑激素（MEL）。此外，持续时间是 夜间梅尔分泌概况的关键特征。西伯利亚人 将研究仓鼠，这种物种表现出戏剧性的季节性 暴露于短期“冬季”后体内脂肪的波动 光周期。这项研究的目的是确定中枢神经系统目标站点 MEL会引发体内脂肪的季节性变化。梅尔的目标部位 将通过确定：1）MEL结合的定位 使用放射自显影并检查环境和荷尔蒙的大脑 对MEL结合的影响（例如，时间，光周期，松果体切除术 [pinx]），2）MEL结合位点的病变是否会消除短暂 日间引起的体重和脂肪，食物摄入和生殖的变化 状态，3）MEL结合部位的病变是否阻止短日反应 通过消除短日MEL信号的接收，通过给出PINX 带有病变的仓鼠编程皮下（S.C.）MEL输注 模仿与转移到短天相关的MEL信号，4）神经 使用新的，高度敏感的目标位点的输入和输出途径 顺行和逆行示踪剂，5）短日反应是否引起 通过编程S.C. MEL输注可以通过选择性损害的封闭 通道或细胞体的纤维切割和神经毒素， 分别在Pinx仓鼠中，6）短日反应是否可以是 直接将MEL直接引起到PINX中的目标位点引起 仓鼠和7）接收MEL信号的神经化学底物 通过免疫细胞化学方法。 这些研究应确定负责的中枢神经系统地点 光周期（MEL）控制几个季节性周期，并添加到我们的 了解环境中自然发生的变化如何 对体内脂肪有巨大影响。神经解剖学的获取 技术将补充跨学科研究计划 首席研究员并为 检查大脑/行为/能量代谢。