Serotonin 2C receptor signaling in a diffuse neuronal network is necessary for LPS anorexia
Serotonin 2C receptor signaling in a diffuse neuronal network is necessary for LPS anorexia
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DOI：
10.1016/j.brainres.2009.09.079
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发表时间：
2010-01-08
期刊：
影响因子：
2.9
通讯作者：
Asarian, Lori
中科院分区：
文献类型：
--
作者：
Kopf, Brigitte S.;Langhans, Wolfgang;Asarian, Lori
LPS 是先天免疫系统的有效激活剂，通常用于研究对感染的急性期反应，包括厌食症。血清素 2C 受体信号传导已被证明参与 LPS 厌食症的介导。在这里，我们使用选择性、强效且具有脑渗透性的血清素 2C 受体拮抗剂 SB 242084 来识别与 LPS 厌食症有关的大脑部位。雄性Long-Evans大鼠在天黑开始时接受1ml/kg腹膜内注射0或0.3mg/kg SB 242084，并在1小时后腹膜内注射0或100μg/kg LPS。注射 LPS 90 分钟后，测量一组大鼠的食物摄入量，并测量另一组未进食的大鼠的 c-Fos 免疫反应性。 SB 242084 显着减弱 LPS 引起的食物摄入量减少，在 LPS 后的前 2 小时内没有明显的厌食症。 SB 242084 还完全阻断了 LPS 诱导的室旁核、杏仁核中央核、孤束核、中缝核和中缝背核中 c-Fos 表达的增加，并部分阻断了延髓腹外侧核和中缝苍白核的 A1 去甲肾上腺素能区域。 SB 242084 没有显着改变弓状核或中缝大核中的 c-Fos 反应。这些数据表明 2C 受体信号传导激活弥漫性神经网络，可能介导厌食症和对 LPS 的其他反应；他们还表明，LPS 后表达 c-Fos 的弓状神经元和中缝大神经元对于 LPS 厌食症不是必需的。 (C) 2009 Elsevier B.V. 保留所有权利。
LPS, a potent activator of the innate immune system, is commonly used to investigate the acute phase response to infection, including anorexia. Serotonin 2C-receptor signaling has been shown to be involved in the mediation of LPS anorexia. Here we used the selective, potent and brain-penetrant serotonin 2C-receptor antagonist SB 242084 to identify the brain sites involved in LPS anorexia. Male Long-Evans rats received 1 ml/kg intraperitoneal injections of 0 or 0.3 mg/kg SB 242084 and intraperitoneal injections of 0 or 100 mu g/kg LPS 1 h later, at dark onset. Food intake was measured in one set of rats and c-Fos immunoreactivity in another, unfed, group 90 min after LPS injection. SB 242084 markedly attenuated the LPS-induced reduction in food intake, with no anorexia evident for the first 2 h after LPS. SB 242084 also completely blocked the LPS-induced increases in c-Fos expression in the paraventricular nucleus, central nucleus of the amygdala, nucleus tractus solitarii, median raphe nucleus and dorsal raphe nucleus and partially blocked it in the A1 noradrenergic area of the ventrolateral medulla and the raphe pallidus nucleus. SB 242084 did not significantly alter the c-Fos response in the arcuate nucleus or the raphe magnus nucleus. These data indicate that 2C receptor signaling activates a diffuse neural network, presumably mediating anorexia and other responses to LPS; they also suggest that the arcuate and the raphe magnus neurons that express c-Fos after LPS are not necessary for LPS anorexia. (C) 2009 Elsevier B.V. All rights reserved.