Concomitant loss of dynorphin, NARP, and orexin in narcolepsy
Concomitant loss of dynorphin, NARP, and orexin in narcolepsy
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DOI：
10.1212/01.wnl.0000168173.71940.ab
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发表时间：
2005-10-25
期刊：
影响因子：
9.9
通讯作者：
Scammell, TE
中科院分区：
文献类型：
--
作者：
Crocker, A;España, RA;Scammell, TE
背景：发作性睡病伴猝倒与食欲素/下丘脑分泌素的丧失有关。据推测，自身免疫过程杀死了产生食欲素的神经元，但这些细胞可能存活下来但无法产生食欲素。目的：检查食欲素神经元的其他标志物是否在发作性睡病伴猝倒中丢失。方法：我们使用免疫组织化学和原位杂交来检测五名对照者和两名发作性睡病患者下丘脑中食欲素、神经元活动调节五聚蛋白（NARP）和强啡肽原的表达。结果：在对照下丘脑中，至少 80% 的产生食欲素的神经元还含有强啡肽原 mRNA 和 NARP。在发作性睡病患者中，产生这些标记物的细胞数量减少至正常人的 5% 至 10% 左右。结论：发作性睡病伴猝倒很可能是由产生食欲素的神经元缺失引起的。此外，强啡肽和神经元活动调节五聚蛋白的丧失可能会导致发作性睡病的症状。
Background: Narcolepsy with cataplexy is associated with a loss of orexin/hypocretin. It is speculated that an autoimmune process kills the orexin-producing neurons, but these cells may survive yet fail to produce orexin. Objective: To examine whether other markers of the orexin neurons are lost in narcolepsy with cataplexy. Methods: We used immunohistochemistry and in situ hybridization to examine the expression of orexin, neuronal activity-regulated pentraxin (NARP), and prodynorphin in hypothalami from five control and two narcoleptic individuals. Results: In the control hypothalami, at least 80% of the orexin-producing neurons also contained prodynorphin mRNA and NARP. In the patients with narcolepsy, the number of cells producing these markers was reduced to about 5 to 10% of normal. Conclusions: Narcolepsy with cataplexy is likely caused by a loss of the orexin-producing neurons. In addition, loss of dynorphin and neuronal activity-regulated pentraxin may contribute to the symptoms of narcolepsy.