Ryu Vitaly, Garretson John T, Liu Yang, Vaughan Cheryl H, Bartness Timothy J
Department of Biology, Center for Obesity Reversal, Neuroscience Institute, Georgia State University, Atlanta, Georgia, 30302-4010.
Department of Biology, Center for Obesity Reversal, Neuroscience Institute, Georgia State University, Atlanta, Georgia, 30302-4010
J Neurosci. 2015 Feb 4;35(5):2181-90. doi: 10.1523/JNEUROSCI.3306-14.2015.
Brown adipose tissue (BAT) is an important source of thermogenesis which is nearly exclusively dependent on its sympathetic nervous system (SNS) innervation. We previously demonstrated the SNS outflow from brain to BAT using the retrograde SNS-specific transneuronal viral tract tracer, pseudorabies virus (PRV152) and demonstrated the sensory system (SS) inflow from BAT to brain using the anterograde SS-specific transneuronal viral tract tracer, H129 strain of herpes simplex virus-1. Several brain areas were part of both the SNS outflow to, and receive SS inflow from, interscapular BAT (IBAT) in these separate studies suggesting SNS-SS feedback loops. Therefore, we tested whether individual neurons participated in SNS-SS crosstalk by injecting both PRV152 and H129 into IBAT of Siberian hamsters. To define which dorsal root ganglia (DRG) are activated by BAT SNS stimulation, indicated by c-Fos immunoreactivity (IR), we prelabeled IBAT DRG innervating neurons by injecting the retrograde tracer Fast Blue (FB) followed 1 week later by intra-BAT injections of the specific β3-adrenoceptor agonist CL316,243 in one pad and the vehicle in the contralateral pad. There were PRV152+H129 dually infected neurons across the neuroaxis with highest densities in the raphe pallidus nucleus, nucleus of the solitary tract, periaqueductal gray, hypothalamic paraventricular nucleus, and medial preoptic area, sites strongly implicated in the control of BAT thermogenesis. CL316,243 significantly increased IBAT temperature, afferent nerve activity, and c-Fos-IR in C2-C4 DRG neurons ipsilateral to the CL316,243 injections versus the contralateral side. The neuroanatomical reality of the SNS-SS feedback loops suggests coordinated and/or multiple redundant control of BAT thermogenesis.
棕色脂肪组织（BAT）是产热的重要来源，其几乎完全依赖于交感神经系统（SNS）的神经支配。我们之前使用逆行性SNS特异性跨神经元病毒示踪剂伪狂犬病病毒（PRV152）证明了从大脑到BAT的SNS传出通路，并使用顺行性SS特异性跨神经元病毒示踪剂单纯疱疹病毒1型H129株证明了从BAT到大脑的感觉系统（SS）传入通路。在这些单独的研究中，几个脑区既是到肩胛间BAT（IBAT）的SNS传出通路的一部分，又接收来自IBAT的SS传入，这表明存在SNS-SS反馈回路。因此，我们通过将PRV152和H129都注射到西伯利亚仓鼠的IBAT中来测试单个神经元是否参与SNS-SS串扰。为了确定哪些背根神经节（DRG）被BAT SNS刺激激活（以c-Fos免疫反应性（IR）表示），我们通过注射逆行示踪剂快蓝（FB）预先标记支配IBAT DRG的神经元，1周后在一个垫中向BAT内注射特异性β3-肾上腺素能受体激动剂CL316,243，在对侧垫中注射溶媒。在整个神经轴上存在PRV152+H129双重感染的神经元，在中缝苍白核、孤束核、导水管周围灰质、下丘脑室旁核和内侧视前区密度最高，这些部位与BAT产热的控制密切相关。与对侧相比，CL316,243注射同侧的C2-C4 DRG神经元中，CL316,243显著提高了IBAT温度、传入神经活动和c-Fos-IR。SNS-SS反馈回路的神经解剖学事实表明对BAT产热存在协调和/或多重冗余控制。
