Central Action of Brain-Derived Neurotrophic Factor in Male and Female Rats

 描述(申请人提供)：肥胖是世界范围内的一个主要健康问题。脑源性神经营养因子(BDNF)是一种神经营养因子，在包括人类在内的许多物种的能量平衡调节中发挥重要作用。因此，脑源性神经营养因子系统可作为防治肥胖的治疗靶点之一。越来越多的证据表明，能量平衡和新陈代谢的调节对两性来说是不同的。以往的研究表明，BDNF可以激活交感神经系统来调节代谢。然而，负责BDNF诱导能量代谢的确切神经回路尚不清楚。此外，女性对脑源性神经营养因子调节能量平衡的作用比男性更敏感。BDNF调节能量代谢的性别差异的潜在神经机制尚不清楚。本项目将研究BDNF系统在调节雄性和雌性大鼠能量代谢方面的潜在神经机制。首先，将确定涉及脑源性神经营养因子的中枢神经系统-外周组织回路。然后评估BDNF对代谢组织交感神经分子标志物和交感神经驱动力的影响。总而言之，该项目将提供直接的神经解剖学、神经功能、分子和神经化学证据，揭示BDNF对新陈代谢和能量平衡的影响机制。此外，该项目将提供有关性别差异的重要新信息，以回应BDNF的治疗。这些信息对于确定针对性别的生物目标进行干预以预防或治疗肥胖症是非常宝贵的。此外，该项目为研究生和本科生提供了大量参与研究的机会，并根据R15的使命改善了迈阿密大学的研究环境。

 DESCRIPTION (provided by applicant): Obesity is a major health problem worldwide. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays essential roles in the regulation of energy balance in many species including humans. Thus, BDNF system could be one of the therapeutic targets for prevention and treatment of obesity. There is increasing evidence that regulation of energy balance and metabolism is not the same for both genders. Previous studies suggest that BDNF activates sympathetic nervous system to regulate metabolism. However, the exact neural circuit responsible for BDNF-induced energy metabolism is unknown. Additionally, females are more sensitive to BDNF's effects on the regulation of energy balance than males. The underlying neural mechanism for the sex differences in energy metabolism regulated by BDNF is unknown. This project will examine potential neural mechanism of BDNF system in regulating energy metabolism in male and female rats. First, the central nervous system-peripheral tissue circuit involving BDNF will be identified. Then changes in specific sympathetic molecular markers and sympathetic drive to metabolic tissues by BDNF administration will be assessed. Collectively, this project will provide direct neuroanatomical, neurofunctional, molecular, and neurochemical evidence underlying the mechanisms of BDNF's effects on metabolism and energy homeostasis. Additionally, this project will provide important new information about sex differences in response to BDNF administration. Such information is invaluable for identifying gender-specific biological targets for intervention to prevent or treat obesity. Furthermore, this project provides plentiful opportunities for graduate and undergraduate students to participate in research and to enhance research environment at Miami University, in agreement with the R15 mission.