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 i nclude: 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.
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