Cano Georgina, Passerin Alicia M, Schiltz Jennifer C, Card J Patrick, Morrison Shaun F, Sved Alan F
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
J Comp Neurol. 2003 Jun 2;460(3):303-26. doi: 10.1002/cne.10643.
The thermogenic activity of interscapular brown adipose tissue (IBAT) in response to physiologic stimuli, such as cold exposure, is controlled by its sympathetic innervation. To determine which brain regions might be involved in the regulation of cold-evoked increases in sympathetic outflow to IBAT, the present study compared central nervous system (CNS) areas activated by cold exposure with brain regions anatomically linked to the sympathetic innervation of IBAT. Immunocytochemical localization of Fos was examined in the brains of rats exposed to 4 degrees C for 4 hours. In a separate group of rats, the neural circuit involved in IBAT control, including the location of sympathetic preganglionic neurons in the spinal cord, was characterized with pseudorabies virus, a retrograde transynaptic tracer. Central noradrenergic and serotonergic groups related to the sympathetic outflow to IBAT also were identified. Localization of viral antigens at different survival times (66-96 hours) revealed infection in circumscribed CNS populations, but only a subset of the regions comprising this circuitry showed cold-evoked Fos expression. The raphe pallidus and the ventromedial parvicellular subdivision of the paraventricular hypothalamic nucleus (PVH), both infected at early survival times, were the main areas containing sympathetic premotor neurons activated by cold exposure. Major cold-sensitive areas projecting to spinal interneurons or to regions containing sympathetic premotor neurons, which became infected at intermediate intervals, included lateral hypothalamic, perifornical, and retrochiasmatic areas, anterior and posterior PVH, ventrolateral periaqueductal gray, and Barrington's nucleus. Areas infected later, most likely related to reception of cold-related signals, comprised the lateral preoptic area, parastrial nucleus, dorsomedial hypothalamic nucleus, lateral parabrachial nucleus, and nucleus of the solitary tract. These interconnected areas, identified by combining functional and retrograde anatomic approaches, likely constitute the central circuitry responsible for the increase in sympathetic outflow to IBAT during cold-evoked thermogenesis.
肩胛间棕色脂肪组织（IBAT）对诸如冷暴露等生理刺激的产热活性受其交感神经支配的控制。为了确定哪些脑区可能参与调节冷刺激引起的流向IBAT的交感神经输出增加，本研究将冷暴露激活的中枢神经系统（CNS）区域与在解剖学上与IBAT交感神经支配相关的脑区进行了比较。在暴露于4℃4小时的大鼠脑中检查了Fos的免疫细胞化学定位。在另一组大鼠中，用伪狂犬病病毒（一种逆行跨突触示踪剂）对参与IBAT控制的神经回路进行了表征，包括脊髓中交感神经节前神经元的位置。还确定了与流向IBAT的交感神经输出相关的中枢去甲肾上腺素能和5-羟色胺能神经组。在不同存活时间（66 - 96小时）对病毒抗原的定位显示，在限定的CNS群体中有感染，但构成该神经回路的区域中只有一部分显示出冷刺激引起的Fos表达。在存活早期均被感染的中缝苍白核和室旁下丘脑核（PVH）的腹内侧小细胞亚区是含有因冷暴露而激活的交感神经运动前神经元的主要区域。在中间间隔期被感染的、投射到脊髓中间神经元或含有交感神经运动前神经元区域的主要冷敏感区域包括下丘脑外侧区、穹窿周区和视交叉后区、PVH的前部和后部、腹外侧导水管周围灰质以及巴林顿核。较晚被感染的区域，很可能与冷相关信号的接收有关，包括视前外侧区、旁星形核、下丘脑背内侧核、臂旁外侧核和孤束核。通过结合功能和逆行解剖学方法确定的这些相互连接的区域，可能构成了在冷刺激产热过程中流向IBAT的交感神经输出增加的中枢神经回路。
