The melanocortinergic pathway is rapidly recruited by emotional stress and contributes to stress-induced anorexia and anxiety-like behavior
The melanocortinergic pathway is rapidly recruited by emotional stress and contributes to stress-induced anorexia and anxiety-like behavior
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DOI：
10.1210/en.2007-0745
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发表时间：
2007-11-01
期刊：
影响因子：
4.8
通讯作者：
Lu, Xin-Yun
中科院分区：
文献类型：
--
作者：
Liu, Jing;Garza, Jacob C.;Lu, Xin-Yun
已知产生黑皮质素受体激动剂（源自阿黑皮素原的α-MSH）和拮抗剂（刺鼠相关蛋白）的神经元对代谢应激（例如食物剥夺和葡萄糖缺乏）敏感。然而，这些神经元如何对情绪/心理压力作出反应仍有待阐明。我们在这里报告说，急性情绪应激，即约束和强迫游泳，诱发mRNA表达的c-fos，神经元激活标记物，在一个高比例的proopiomelanocortin神经元（高达53%的约束压力和62%的强迫游泳），具有显着的变化沿着的喙尾轴的弓状核。相比之下，只有一小部分与刺豚鼠相关的蛋白质神经元在这个大脑区域被激活。这些神经元激活模式与行为反应相关。这两种应激源抑制进食和诱导焦虑样行为的高架十字迷宫测试，反映了在开放臂的条目和时间的百分比减少。中枢预处理SHU 9119，一种黑皮质素受体拮抗剂，剂量依赖性地减弱急性束缚或强迫游泳引起的厌食和焦虑作用。这些结果表明，黑素皮质素能通路可以迅速招募急性情绪应激，黑素皮质素信号的激活参与介导应激诱导的厌食症和焦虑。
Neurons producing melanocortin receptor agonist, alpha-MSH derived from proopiomelanocortin, and antagonist, agouti-related protein, are known to be sensitive to metabolic stress such as food deprivation and glucoprivation. However, how these neurons respond to emotional/psychological stress remained to be elucidated. We report here that acute emotional stressors, i.e. restraint and forced swim, evoked mRNA expression of c-fos, a neuronal activation marker, in a high percentage of proopiomelanocortin neurons (up to 53% for restraint stress and 62% for forced swim), with marked variations along the rostro-caudal axis of the arcuate nucleus. In contrast, only a small population of agouti-related protein neurons in this brain region was activated. These neuronal activation patterns were correlated with behavioral reactions. Both stressors suppressed feeding and induced anxiety-like behavior in the elevated plus-maze test, as reflected by a reduction in the percentage of entries and time spent in the open arms. Central pretreatment with SHU9119, a melanocortin receptor antagonist, dose dependently attenuated the anorectic and anxiogenic effects elicited by acute restraint or forced swim. These results indicate that the melancortinergic pathway can be rapidly recruited by acute emotional stress, and that activation of melanocortin signaling is involved in mediating stress-induced anorexia and anxiety.