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

基本信息

批准号：
6185258
负责人：
Timothy Jon Bartness
金额：
$ 6.07万
依托单位：
GEORGIA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-04-01 至 2001-03-31
项目状态：
已结题

项目摘要

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?

该赠款提案的目的是开发新颖的范式，获取新技术并将其应用于当前研究的扩展主题或与这些主题相关的新研究努力进一步发展PI的职业。提出了三个具体目标，每个都有一组实验。特定目的I：脂肪组织神经的作用是什么季节性肥胖的光周期控制？提出了实验扩展我们最近关于白脂肪组织直接支配的报告（WAT）通过交感神经系统（SNS）和我们的感觉的发现 WAT的神经（请参阅初步研究），并且每个研究的作用西伯利亚仓鼠中季节性肥胖的光周期控制。四个问题将得到回答：1）短日期引起的身体可以减少脂肪独立于WAT的SN神经？2）相对分开的SNS WAT的神经支配在中枢神经系统中融合？，3）什么 WAT的感觉神经的范围是？4）在短日期引起的WAT感觉神经的功能作用减少体内脂肪？特定目标II：总体量之间的关系是什么脂肪和ho积的水平以及感觉神经的作用在这种关系中发挥作用？西伯利亚仓鼠似乎通过增加外部存储的能量来响应体内脂肪的减少食物ho积的形式。自然发生并实验诱导体内脂肪减少将用于进一步测试逆全身脂肪与ho积食物之间的关系西伯利亚仓鼠，以及WAT的感觉神经的作用关系。将使用模拟洞穴研究食物ho积系统。将回答三个问题：1）做短暂的一天体内脂肪的减少刺激食物ho积了？，2）部分手术是否会脂肪切除术（去除脂肪）刺激食物ho积了？和3）在短日期引起的水平上的感官神经支配 ho积食物？特定目标III：可以使用C-FOS活动来识别功能褪黑激素信号的接收/传播和thefr传播的位点投影字段？提出了实验来检验以下假设刺激推定位点接收/传播褪黑激素信号会激活直接的基因C-FOS。这将是通过使用计时的Infision范例来完成皮下或脑内编程的生理相关褪黑激素的递送向松果体切除的西伯利亚仓鼠的信号。三个问题将是回答：1）褪黑激素的全身输注激活神经元三个在西伯利亚仓鼠中显示褪黑激素结合的大脑部位和这些细胞的神经递质表型是什么？，2）被褪黑激素激活的细胞的传出投影场并位于显示褪黑激素结合的三个大脑部位，3）可以使用逆行验证这些推定的传出投影场道跟踪结合C-FOS免疫细胞化学技术？