Annual Rhythms of Energy Balance and Behavior

描述（由申请人提供）：总体目标是表征下丘脑神经肽Y机制在控制日常麻木中发挥的作用，这是一种极端形式的温度调节，进化以帮助动物应对有限的食物供应。将探讨整合整体能量平衡和麻痹的中枢和外周神经机制。食物摄入量和体重，繁殖，和每日的麻木的年度节奏在西伯利亚仓鼠（Photopus sungorus），在所有实验的模式物种有很好的记录。具体目标包括：1）测量和对比迟钝和非迟钝的西伯利亚仓鼠的下丘脑神经肽和神经肽mRNA水平，特别是神经肽Y; 2）检查用神经肽Y受体拮抗剂预处理是否可以防止自发和/或2DG诱导的迟钝; 3）确定连续的NPY输注是否产生延长的低温; 4）评估通过阻断棕色脂肪组织的去甲肾上腺素受体来抑制产热是否产生类似于torpore的低体温。 关于控制能量平衡和体温调节的生理机制，我们还有很多不了解的地方。描述特定神经通路和神经递质之间的相互作用，以及西伯利亚仓鼠等模型系统中的日常麻木，可以为哺乳动物特别是人类的这些过程的调节提供重要的见解。深入了解可逆性低温的机制具有重要的医学意义。在许多类型的大手术中，尤其是器官移植中，与体温过低同时发生的代谢、血流等减少可能非常有益。西伯利亚仓鼠和其他几个物种经历对人类和大多数其他哺乳动物致命的体温过低的机制目前还知之甚少。拟议的研究解决了调节生物学的基本问题，从而提供了建立适用于所有哺乳动物的一般原则的机会。

DESCRIPTION (provided by applicant): The overall goal is to characterize the role that hypothalamic neuropeptide Y mechanisms play in controlling daily torpor, an extreme form of temperature regulation that evolved to help animals contend with limited food availability. The central and peripheral neural mechanisms integrating overall energy balance and torpor will be explored. Annual rhythms of food intake and body mass, reproduction, and daily torpor are well documented in the Siberian hamster (Phodopus sungorus), the model species in all experiments. Specific aims include: 1) measuring and contrasting hypothalamic neuropeptide and neuropeptide mRNA levels, especially neuropeptide Y, in torpid and non-torpid Siberian hamsters; 2) examining whether pretreatment with a neuropeptide Y receptor antagonist can prevent spontaneous and/or 2DG-induced torpor; 3) determining whether successive NPY infusions produce prolonged hypothermia; 4) evaluating whether inhibiting thermogenesis by blocking norepinephrine receptors at brown adipose tissue produces torpor-like hypothermia. Much remains that we do not understand about the physiological mechanisms underlying the control of energy balance and thermoregulation. Delineating the interaction between specific neural pathways and neurotransmitters and daily torpor in a model system like the Siberian hamster could provide important insights into the regulation of these processes for mammals in general and humans in particular. A better understanding of the mechanisms of reversible hypothermia is of medical import. The reduced metabolism, blood flow, etc. coincident with hypothermia may be very beneficial during many types of major surgery, especially organ transplants. Little is known at this time of the mechanism that allows Siberian hamsters and several other species to undergo hypothermia which is lethal to humans and most other mammals. The proposed research addresses fundamental questions in regulatory biology and, thereby, affords the opportunity of establishing general principles applicable to all mammals.