CNS MELATONIN TARGETS AND PHOTOPERIOD-INDUCED OBESITY

这项赠款提案是对ADAMHA RSDA(II级)的申请。人类和 其他动物的体重会有季节性变化。环境问题 这种反应和某些季节繁殖周期的信号 物种是昼夜变化的，其神经内分泌转导是 松果腺及其激素褪黑激素(Mel)。此外，持续时间为 夜间MEL分泌物的关键特征。西伯利亚人 将对仓鼠进行研究，这是一种具有戏剧性季节性的物种 暴露在短暂的“冬日般的”环境中的体脂波动 光周期。本研究的目的是确定中枢神经系统的目标部位 会引发身体脂肪的季节性变化。MEL的目标位置 将通过确定：1)MEL结合在 用放射自显影检查环境和荷尔蒙 对MEL结合的影响(例如，一天中的时间、光周期、松果体切除 [Pinx])，2)MEL结合部位的损伤是否会消除短 白天引起的体重和脂肪、食物摄入量和生殖能力的变化 状态，3)MEL结合部位的损伤是否阻止短日反应 通过给PINX消除短日MEL信号的接收 仓鼠皮下程序性病变(S.C.)梅尔注入了 模拟与短日转换相关的MEL信号，4)神经 使用新的、高度敏感的目标站点的输入和输出路径 顺行和逆行示踪，5)是否诱发短日反应 由编程的S.C.MEL的输注可以通过选择性损伤 传代纤维或细胞体被微刀切割和神经毒素， 分别在Pinx仓鼠中，6)短日照反应是否可以 将MEL直接微量注入松树靶点的研究 仓鼠，以及7)接收MEL信号的神经化学底物 通过免疫细胞化学方法。 这些研究应该确定中枢神经系统站点(S)负责 光周期(MEL)控制几个季节周期，并增加我们的 理解自然发生的环境变化如何 对身体脂肪有显著影响。神经解剖学的习得 技术将补充大学的跨学科研究计划 首席研究员并为以下方面创造独特的研究环境 检查大脑/行为/能量代谢。

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.