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.

本拨款提案是对 ADAMHA RSDA（II 级）的请求。人类和 其他动物的体重也会出现季节性变化。环境 这种反应和某些季节繁殖周期的信号 物种是日长变化，其神经内分泌传感器是 松果体及其激素褪黑激素（MEL）。此外，持续时间为 夜间 MEL 分泌谱的关键特征。西伯利亚 将研究仓鼠，这是一种表现出戏剧性季节性的物种 经历短暂的“冬季”后体内脂肪的波动 光周期。这项研究的目标是确定中枢神经系统目标位点 MEL 会引发体内脂肪的季节性变化。 MEL 的靶位点 将通过确定以下内容来识别：1) MEL 结合的定位 使用放射自显影术检查大脑并检查环境和荷尔蒙 对 MEL 结合的影响（例如，一天中的时间、光周期、松果体切除术 [PINX]), 2) MEL结合位点的损伤是否会消除短 白天引起的体重和脂肪、食物摄入和生殖的变化 状态，3) MEL 结合位点的损伤是否会阻碍短日反应 通过给予 PINX 消除短日 MEL 信号的接收 对患有病变的仓鼠进行皮下 (s.c.) MEL 输注， 模拟与短日转移相关的 MEL 信号，4) 神经 使用新的、高度灵敏的方法检测目标位点的输入和输出途径 顺行和逆行示踪剂，5) 是否引发短日反应 通过编程 s.c. MEL 输注可以通过选择性损伤来阻断 带有微刀切口和神经毒素的通道纤维或细胞体， 分别在 PINX 仓鼠中，6) 短日反应是否可以 通过将 MEL 直接微量输注到 PINX 的靶位点来引发 仓鼠，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 光周期（MEL）控制几个季节周期并添加到我们的 了解环境中自然发生的变化如何影响 对身体脂肪有显着的影响。神经解剖学的获取 技术将补充该中心的跨学科研究计划 首席研究员并为他们创造独特的研究环境 检查大脑/行为/能量代谢。