GLUCOSE METABOLISM EFFECTS ON REPRODUCTIVE BEHAVIOR

描述(改编自申请人的摘要)：能源可用性是 最重要的是控制繁殖的所有环境因素。 减少食物摄入量，减少体内脂肪含量，增加锻炼 对生育力、排卵周期和性行为的显著影响 几乎每一种被研究的雌性哺乳动物，包括女性。的总目标是 拟议的研究是为了了解监测到的感觉系统 细胞能量的可获得性，并抑制繁殖。具体目标 是为了更好地理解代谢刺激的本质，解剖学上的 它们的探测器的位置，以及从探测器到 控制生殖周期和行为的大脑区域。为了拍一张照片 在涉及的大脑区域中，研究人员将检查 不同代谢处理对神经激活的影响(用类FOS测量 免疫反应)遍及整个大脑。特别感兴趣的领域将 检查他们对葡萄糖药物抑制剂的剂量反应 利用率。为了考察这些区域的功能意义，核团 或亚核在反应中表现出神经激活的显著变化 来研究代谢抑制药是否缺乏这些 减弱或阻止代谢抑制剂对发情的影响的区域 周期性(前凸和阴道分泌物)。标准的追踪方法 追踪将被用来确定来自尾部大脑的神经通路 疑似参与搏动性促性腺激素释放激素的下丘脑神经元的干细胞 叙利亚仓鼠的分泌物。另一组实验将检验 比较不同代谢能力对代谢信号性质的影响 脑室注射底物对抗2-DG诱导 发情期。上述实验涉及发表的技术和 在私家侦探的实验室里开始运作。这个实验中的最后一个实验 建议将采取第一个根源，以审查实际 特异性代谢搏动性促黄体生成素分泌和/或神经内分泌效应 促性腺激素释放激素神经元的神经激活。 了解代谢对行为的影响具有广泛的临床意义。 例如，不孕不育总是与身体过度有关。 女性减肥。对所有上述现象的理解将会 通过专注于体重之间联系的研究来促进， 营养、运动和生育能力。然而，新陈代谢的相互作用 对神经系统的影响远远超出了 体重和生育能力之间的联系。尽管我们几乎一无所知 新陈代谢感官的刺激和检测器，似乎是这种感官 制度几乎影响到包括性行为在内的每一类行为， 进食、攻击性、母性行为和学习以及生理 确保热量动态平衡的过程。此外，新陈代谢效应 可能是行为和情绪障碍的基础，例如 老年痴呆症、焦虑症和抑郁症。拟议中的实验将是一个 向理解这些基础生物学迈出的重要一步 现象。

DESCRIPTION (Adapted from applicant's abstract): Energy availability is the most important of all environmental factors that control reproduction. Decreased food intake, body fat content, and increased exercise have dramatic effects on fertility, ovulatory cycles and sex behavior in virtually every female mammal studied, including women. The general goal of the proposed research is to understand the sensory system that monitors cellular energy availability and inhibits reproduction. The specific goals are to better understand the nature of metabolic stimuli, the anatomical location of their detectors, and the neural pathways from the detectors to brain areas controlling reproductive cycles and behavior. To get a picture of the brain areas involved, the investigators will examine the effects of various metabolic treatments on neural activation (as measured by FOS-like immunoreactivity) throughout the brain. Areas of particular interest will be examined for their dose response to pharmacological inhibitors of glucose utilization. To examine the functional significance of these areas, nuclei or subnuclei that show significant changes in neural activation in response to metabolic inhibitors will be lesioned to see whether the absence of these areas attenuate or prevent the effects of metabolic inhibitors on estrous cyclicity (lordosis and the vaginal discharge). Standard methods of tract tracing will be used to determine the neural pathways from the caudal brain stem to the hypothalamic neurons suspected to be involved in pulsatile GnRH secretion in Syrian hamsters. Another set of experiments will examine the nature of metabolic signals by comparing the ability of different metabolic substrates infused intracerebroventricularly to overcome 2-DG-induced anestrus. The above experiments involve techniques that are published and up-and-running in the PI's laboratory. The last experiments in this proposal will take the first stems toward examining the actual neuroendocrine effects of specific metabolic pulsatile LH secretion and/or neural activation in GnRH neurons. Understanding metabolic effects on behavior has broad clinical significance. For example, infertility is consistently associated with excessive body weight loss in women. An understanding of all of the above phenomena will be facilitated by research focused on the links among body weight, nutrition, exercise and fertility. However, the interaction of metabolic fuels with the nervous system has implications that reach far beyond the link between body weight and fertility. Although we know almost nothing of the stimuli and detectors for metabolic sense, it appears that this sensory system influences virtually every category of behavior including sex, eating, aggression, maternal behavior and learning and the physiological processes that insure caloric homeostasis. In addition, metabolic effects on the nervous system might underlie behavioral and mood disorders such as Alzheimer, anxiety and depression. The proposed experiments will be an important step toward understanding the basic biology that underlies these phenomena.