CNS MELATONIN TARGETS AND PHOTOPERIOD-INDUCED OBESITY

这项赠款提案的目的是开发新的范例，获得 新技术，并将它们应用于当前研究的任一扩展 主题或与这些主题相关的新的研究努力，以便 进一步发展政协事业。提出了三个具体目标， 每个人都有一套实验。 具体目标I：脂肪组织的神经支配在 季节性肥胖的光周期控制？建议进行实验，以 扩展我们最近关于白色脂肪组织直接神经支配的报道 交感神经系统(SNS)和我们对感觉的发现(WAT) Wat的神经支配(见初步研究)，以及每种神经的作用。 西伯利亚仓鼠季节性肥胖的光周期控制。四 问题将会被回答：1)短日照会导致身体衰退吗？ 脂肪的发生独立于Wat？的SNS神经支配，2) Wat的相对独立的SNS神经支配汇聚在CNS？，3)什么 Wat的感觉神经支配的范围是什么？以及4)什么是 Wat感觉神经支配在短日照诱导中的作用 减少身体脂肪？ 具体目标二：全身的量与 脂肪和食物囤积水平以及感觉神经的作用 脂肪组织在这段关系中扮演了什么角色？西伯利亚仓鼠似乎 通过增加体内储存的能量来应对体内脂肪的减少 储藏食物的形式。自然发生和实验诱导 身体脂肪的减少将被用来进一步测试相反的情况 人体总脂肪与食物囤积水平的关系 西伯利亚仓鼠，以及Wat感觉神经在其中的作用 两性关系。将使用模拟洞穴来研究囤积食物 系统。将回答三个问题：1)短日照是否由 身体脂肪的减少会刺激食物囤积吗？2)做部分手术 脂肪切除(脂肪去除)刺激食物囤积？3)有什么作用？ 短日照对Wat感觉神经支配的影响 囤积食物？ 具体目标三：c-Fos活性能否用于识别功能性 褪黑素信号的接收/发送位置和传出 投影场？有人提议用实验来检验这一假设 刺激假定用于接收/发送的地点 褪黑素信号激活即刻早期基因c-Fos。这将是 通过使用皮下或皮下组织的定时注射范例实现 生理相关褪黑素的脑内程序化递送 给松果体摘除的西伯利亚仓鼠的信号。将有三个问题 回答：1)全身注射褪黑激素是否会激活大脑中的神经元 西伯利亚仓鼠中显示褪黑激素结合的三个大脑部位和 这些细胞的神经递质表型是什么？2)这些细胞的 褪黑素激活细胞的传出投射野 位于显示褪黑激素结合的三个大脑部位，以及3) 这些假定的传出投影场可以用逆行来验证吗？ 结合c-Fos免疫细胞化学技术的轨迹追踪？

The purpose of this grant proposal is to develop novel paradigms, acquire new techniques and apply them to either extensions of current research themes or to new research endeavors related to these themes in order to develop further the career of the PI. Three Specific Aims are proposed, each with a set of experiments. Specific Aim I: What is the role of the innervation of adipose tissue in the photoperiodic control of seasonal obesity? Experiments are proposed to extend our recent report of the direct innervation of white adipose tissue (WAT) by the sympathetic nervous system (SNS) and our finding of sensory innervation of WAT (see Preliminary Studies), and the role of each in the photoperiodic control of seasonal obesity in Siberian hamsters. Four questions will be answered: 1) Can the short day-induced decreases in body fat occur independently of the SNS innervation of WAT?, 2) Does the relatively separate SNS innervation of WAT converge in the CNS?, 3) What is the extent of the sensory innervation of WAT?, and 4) What is the functional role of the sensory innervation of WAT in the short day-induced decreases in body fat? Specific Aim II: What is the relationship between the amount of total body fat and level of food hoarding and what role does the sensory innervation of adlpose tissue play in this relationship? Siberian hamsters appear to respond to decreases in body fat by increasing externally stored energy in the form of a food hoard. Naturally occurring and experimentally induced decreases in body fat will be used to test further the inverse relationship between total body fat and the level of food hoarding in Siberian hamsters, and the role of the sensory innervation of WAT in this relationship. Food hoarding will be studied using a simulated burrow system. Three questions will be answered: 1) Do the short day-induced decreases in body fat stimulate food hoarding?, 2) Does partial surgical lipectomy (fat removal) stimulate food hoarding?, and 3)What is the role of the sensory innervation of WAT on the short day-induced increases in food hoarding? Specific Aim III: Can c-Fos activity be used to identify the functional sites of reception/transmission of melatonin signals and thefr efferent projection fields? Experiments are proposed to test the hypothesis that stimulation of the putative sites for the reception/transmission of melatonin signals activates the immediate-early gene c-Fos. This will be accomplished by using the timed infision paradigm for the subcutaneous or intracerebral programmed delivery of physiologically relevant melatonin signals to pinealectomized Siberian hamsters. Three questions will be answered: 1)Do systemic infusions of melatonin activate neurons in the three brain sites that show melatonin binding in Siberian hamsters and what are the neurotransmitter phenotypes of these cells?, 2) Where are the efferent projection fields of the cells that are activated by melatonin and located in the three brain sites that show melatonin binding?, and 3) Can these putative efferent projection fields be verified using retrograde tract tracing combined with c-Fos immunocytochemical techniques?