Lipopolysaccharide challenge-induced suppression of Fos in hypothalamic orexin neurons: Their potential role in sickness behavior
Lipopolysaccharide challenge-induced suppression of Fos in hypothalamic orexin neurons: Their potential role in sickness behavior
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DOI：
10.1016/j.bbi.2009.03.005
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发表时间：
2009-10-01
影响因子：
15.1
通讯作者：
Goehler, Lisa E.
中科院分区：
文献类型：
--
作者：
Gaykema, Ronald P. A.;Goehler, Lisa E.
下丘脑外侧区的食欲素神经元是调节清醒、进食和奖赏相关行为的重要组成部分。在这项研究中，我们研究了脂多糖（LPS）的挑战对Fos的表达在食欲素神经元在大鼠的影响，以确定在两种不同的行为背景下的疾病期间的变化。一组大鼠在白天用盐水或LPS处理，然后在高架十字迷宫（高架十字迷宫，elevated plus maze）上测试或留在其家笼中直至处死。另一组在黑暗开始前不久接受LPS或盐水，并在黑暗期90分钟处死。对脑进行Fos和食欲素-A免疫反应性（两个队列）以及Fos和组氨酸脱羧酶（黑暗期队列）的双重染色。食欲素神经元在探索行为的背景下被强烈激活（在内侧和外侧部分中对Fos进行双标记）。迷宫暴露前的LPS挑战减少了这种激活，最明显的是在外侧食欲素神经元。在家庭笼控制，LPS的挑战导致增加Fos的表达，最显着的是在内侧食欲素神经元相比，盐水注射的家庭笼控制，显示很少或没有Fos在白天。在黑暗期，Fos在食欲素和组胺能神经元的表达丰富，LPS攻击强烈抑制。这些发现与以下假设一致：食欲素神经元与组胺能系统一起代表神经回路的潜在靶点，该神经回路可能通过这些下丘脑细胞群的功能抑制而驱动由于外周炎症引起的疾病行为。(C)2009 Elsevier Inc. All rights reserved.
Orexin neurons in the lateral hypothalamus constitute a critical component in regulation of waking, feeding, and reward-related behaviors. In this study we examined the effects of lipopolysaccharide (LPS) challenge on Fos expression in orexin neurons in rats, to determine changes during sickness in two different behavioral contexts. One cohort of rats was treated with saline or LPS during the daytime, and then tested on an elevated plus maze (EPM) or left in their home cage until sacrifice. Another cohort received LPS or saline shortly before dark onset and was sacrificed 90 min into the dark period. The brains were double-stained for Fos and orexin-A immunoreactivity (both cohorts) and for Fos and histidine decarboxylase (dark period cohort). Orexin neurons were strongly activated in context of exploratory behavior (double-labeled for Fos in both medial and lateral portions). LPS challenge prior to maze exposure diminished this activation, most notably among the lateral orexin neurons. In home cage controls, LPS challenge lead to increased Fos expression, most notably in the medial orexin neurons, when compared to saline-injected home cage controls that show little or no Fos during the daytime. In the dark period, Fos expression in both orexin and histaminergic neurons was abundant, which LPS challenge strongly suppressed. These findings are consistent with the hypothesis that the orexin neurons, in conjunction with the histaminergic system, represent a potential target of the neurocircuitry that drives sickness behavior due to peripheral inflammation, likely through functional inhibition of these hypothalamic cell groups. (C) 2009 Elsevier Inc. All rights reserved.