PDF(Pubmed)
Abstract：
Orexin/hypocretin terminals innervate the dorsal raphe nucleus (DRN), which projects to motor control areas important for spontaneous physical activity (SPA) and energy expenditure (EE). Orexin receptors are expressed in the DRN, and obesity-resistant (OR) rats show higher expression of these receptors in the DRN and elevated SPA/EE. We hypothesized that orexin-A in the DRN enhances SPA/EE and that DRN-GABA modulates the effect of orexin-A on SPA/EE. We manipulated orexin tone in the DRN either through direct injection of orexin-A or through the chemogenetic activation of lateral-hypothalamic (LH) orexin neurons. In the orexin neuron activation experiment, fifteen minutes prior to the chemogenetic activation of orexin neurons, the mice received either the GABA-agonist muscimol or antagonist bicuculline injected into the DRN, and SPA/EE was monitored for 24 h. In a separate experiment, orexin-A was injected into the DRN to study the direct effect of DRN orexin on SPA/EE. We found that the activation of orexin neurons elevates SPA/EE, and manipulation of GABA in the DRN does not alter the SPA response to orexin neuron activation. Similarly, intra-DRN orexin-A enhanced SPA and EE in the mice. These results suggest that orexin-A in the DRN facilitates negative energy balance by increasing physical activity-induced EE, and that modulation of DRN orexin-A is a potential strategy to promote SPA and EE.
摘要：
Orexin/hypocretin末端支配背侧中缝核（DRN），该项目用于对自发身体活动（SPA）和能量消耗（EE）重要的运动控制区域。食欲素受体在DRN中表达，和肥胖抵抗（OR）大鼠在DRN中这些受体的表达更高，SPA/EE升高。我们假设DRN中的食欲素A增强SPA/EE，而DRN-GABA调节食欲素A对SPA/EE的影响。我们通过直接注射orexin-A或通过下丘脑外侧（LH）orexin神经元的化学遗传激活来操纵DRN中的orexin音调。在食欲素神经元激活实验中，在食欲素神经元的化学激活前15分钟，小鼠接受注射到DRN中的GABA激动剂麝香酚或拮抗剂bicuculline，和SPA/EE监测24小时。在一个单独的实验中，将orexin-A注射到DRN中，以研究DRNorexin对SPA/EE的直接影响。我们发现食欲素神经元的激活会升高SPA/EE，DRN中GABA的操作不会改变SPA对食欲素神经元激活的反应。同样，DRN内食欲素A增强小鼠的SPA和EE。这些结果表明，DRN中的食欲素A通过增加体力活动引起的EE来促进负能量平衡，调节DRN食欲素-A是促进SPA和EE的潜在策略。
