Identification of sympathetic premotor neurons in medullary raphe regions mediating fever and other thermoregulatory functions
Identification of sympathetic premotor neurons in medullary raphe regions mediating fever and other thermoregulatory functions
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DOI：
10.1523/jneurosci.1219-04.2004
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发表时间：
2004-06-09
影响因子：
5.3
通讯作者：
Kaneko, T
中科院分区：
文献类型：
--
作者：
Nakamura, K;Matsumura, K;Kaneko, T
交感神经前运动神经元直接控制胸段脊髓中间外侧细胞柱（IML）中的交感神经节前神经元（SPN），并且这些运动前神经元中的许多位于延髓。延髓头端腹外侧区含有控制心血管状况的运动前神经元，而延髓头端中缝区是交感运动前神经元的候选来源，用于体温调节功能。在这里，我们表明，这些延髓中缝区域包含推定的神经元，这些神经元直接控制体温调节SPN。表达囊泡谷氨酸转运体3（VGLUT 3）的神经元分布在大鼠延髓中缝区域，包括中缝大核和头端中缝苍白核，大多缺乏5-羟色胺免疫反应。这些VGLUT 3阳性神经元表达Fos的冷暴露或中央管理的前列腺素E-2，热原介质。将伪狂犬病病毒接种到肩胛间棕色脂肪组织（BAT）或尾部后的跨神经元逆行标记表明，这些表达VGLUT 3的延髓中缝神经元通过特定胸段的SPN多突触地支配这些体温调节效应器，并且将谷氨酸微量注射到BAT控制段的IML中产生BAT产热。顺行追踪研究进一步表明，这些VGLUT 3表达的延髓中缝神经元的树突的SPN的直接投影。此外，内IML应用谷氨酸受体拮抗剂阻断BAT产热触发的延髓中缝区域的去抑制。目前的研究结果表明，VGLUT 3表达神经元在延髓中缝区域构成兴奋性神经元，可以被归类为一个新的组的交感神经运动前神经元的体温调节功能，包括发烧。
Sympathetic premotor neurons directly control sympathetic preganglionic neurons (SPNs) in the intermediolateral cell column (IML) of the thoracic spinal cord, and many of these premotor neurons are localized in the medulla oblongata. The rostral ventrolateral medulla contains premotor neurons controlling the cardiovascular conditions, whereas rostral medullary raphe regions are a candidate source of sympathetic premotor neurons for thermoregulatory functions. Here, we show that these medullary raphe regions contain putative glutamatergic neurons and that these neurons directly control thermoregulatory SPNs. Neurons expressing vesicular glutamate transporter 3 (VGLUT3) were distributed in the rat medullary raphe regions, including the raphe magnus and rostral raphe pallidus nuclei, and mostly lacked serotonin immunoreactivity. These VGLUT3-positive neurons expressed Fos in response to cold exposure or to central administration of prostaglandin E-2, a pyrogenic mediator. Transneuronal retrograde labeling after inoculation of pseudorabies virus into the interscapular brown adipose tissue (BAT) or the tail indicated that those VGLUT3-expressing medullary raphe neurons innervated these thermoregulatory effector organs multisynaptically through SPNs of specific thoracic segments, and microinjection of glutamate into the IML of the BAT-controlling segments produced BAT thermogenesis. An anterograde tracing study further showed a direct projection of those VGLUT3-expressing medullary raphe neurons to the dendrites of SPNs. Furthermore, intra-IML application of glutamate receptor antagonists blocked BAT thermogenesis triggered by disinhibition of the medullary raphe regions. The present results suggest that VGLUT3-expressing neurons in the medullary raphe regions constitute excitatory neurons that could be categorized as a novel group of sympathetic premotor neurons for thermoregulatory functions, including fever.