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

 描述（由申请人提供）：肥胖是全球范围内的主要健康问题。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，BDNF系统可能成为肥胖防治的治疗靶点之一。越来越多的证据表明，男女对能量平衡和新陈代谢的调节是不一样的。以往的研究表明BDNF激活交感神经系统调节代谢。然而，负责BDNF诱导的能量代谢的确切神经回路是未知的。此外，女性对BDNF在能量平衡调节方面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。本研究将探讨BDNF系统在调节雄性和雌性大鼠能量代谢中的潜在神经机制。首先，将确定涉及BDNF的中枢神经系统-外周组织回路。然后将评估特定交感神经分子标记物的变化和BDNF给药对代谢组织的交感神经驱动。总的来说，这个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的BDNF的代谢和能量稳态的影响机制。此外，该项目将提供重要的新信息，性别差异，在响应BDNF管理。这些信息对于确定预防或治疗肥胖的干预措施的性别特异性生物靶点非常宝贵。此外，该项目提供了丰富的机会，研究生和本科生参与研究，并加强研究环境在迈阿密大学，在协议的R15使命。

 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.