CNS MELATONIN TARGETS AND PHOTOPERIOD-INDUCED OBESITY

本赠款提案是ADAMHA RSDA（二级）的申请。人类和 其他动物的体重也有季节性变化。环境 这种反应和季节性繁殖周期的信号， 物种的主要生理机制是日长变化，其神经内分泌传导因子是 松果体及其激素褪黑素（MEL）。此外，持续时间为 夜间MEL分泌特征的关键特征。西伯利亚 仓鼠将被研究，一个物种，表现出戏剧性的季节性 暴露于短暂的“冬季样”后体内脂肪的波动 光周期本研究的目的是确定中枢神经系统的靶点 引发身体脂肪的季节性变化。MEL的靶位点 将通过确定：1）MEL结合在 大脑使用放射自显影和检查环境和激素 对MEL结合的影响（例如，时辰，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 日引起的体重和脂肪、摄食量和生殖 状态，3）MEL结合位点的损伤是否阻断短日照反应 通过给出PINX来消除短日照MEL信号的接收， 皮下（s.c.）程控的带有病变的仓鼠MEL输注， 模拟与转移到短日照相关的MEL信号，4）神经 输入和输出途径的目标网站使用新的，高度敏感的 顺行和逆行示踪剂，5）是否引起短日反应 通过编程的s.c. MEL输注可以通过选择性损伤 通道纤维或细胞体被显微刀切割和神经毒素， 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中的靶位点中而引发 仓鼠，以及7）接收MEL信号的神经化学底物 免疫细胞化学方法。 这些研究应确定CNS部位， 光周期（MEL）控制的几个季节性周期，并添加到我们的 了解环境中自然发生的变化 对身体脂肪有显著的影响。神经解剖学的获得 技术将补充跨学科的研究计划， 首席研究员，并创造一个独特的研究环境， 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.