Hypocretin (orexin) loss in Parkinson's disease
Hypocretin (orexin) loss in Parkinson's disease
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DOI：
10.1093/brain/awm090
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发表时间：
2007-06-01
期刊：
影响因子：
14.5
通讯作者：
Swaab, Dick F.
中科院分区：
文献类型：
--
作者：
Fronczek, Rolf;Overeem, Sebastiaan;Swaab, Dick F.
下丘脑降克素系统在包括睡眠/觉醒调节和新陈代谢在内的各种功能的调节中起着核心作用。鉴于帕金森氏病(PD)中睡眠障碍等非运动症状的高患病率，人们对帕金森病(PD)中的下丘脑泌素功能越来越感兴趣。然而，测量脑脊液下丘脑分泌素水平的研究得出了相互矛盾的结果。在帕金森病患者和匹配的对照组中，我们(I)使用免疫细胞化学和图像分析系统估计了死后下丘脑中下丘脑中的下丘脑神经元的数量；(Ii)用放射免疫分析法定量了死后脑室脑脊液中的下丘脑中的下丘脑神经元数；(Iii)用放射免疫法测定了前额叶皮质中的下丘脑下丘脑下克汀神经元的数量。此外，在下丘脑下丘脑下克体细胞区证实了路易小体的存在。结果显示，帕金森病患者脑室脑脊液中的下丘脑-I含量(PD：365.5 pg/ml(328.0-448.3)；对照组：483.5(433.5-512.3)；PD：20276(13821-31229)；对照组：36842(32546-50938)；P=0.016)显著低于对照组。(3)前额叶皮质的下丘脑肌酸-I浓度(PD：389.6 pg/g(249.2-652.2)；对照组：676.6(4675-883.9)；P=0.043)。帕金森病患者的下丘脑神经传递受到影响。帕金森病患者前额叶皮质的下丘脑-I浓度降低了近40%，而脑室脑脊液水平降低了近25%。与对照组相比，下丘脑克汀神经元的总数几乎减半。
The hypothalamic hypocretin (orexin) system plays a central role in the regulation of various functions, including sleep/wake regulation and metabolism. There is a growing interest in hypocretin function in Parkinson's disease (PD), given the high prevalence of non-motor symptoms such as sleep disturbances in this disorder. However, studies measuring CSF hypocretin levels have yielded contradictory results. In PD patients and matched controls, we (i) estimated the number of hypocretin neurons in post-mortem hypothalami using immunocytochemistry and an image analysis system (ii) quantified hypocretin levels in post-mortem ventricular CSF and (iii) prefrontal cortex using a radioimmunoassay. Furthermore, presence of Lewy bodies was verified in the hypothalamic hypocretin cell area. Data are presented as median (25th-75th percentile).We showed a significant decrease between PD patients and controls in (i) the number of hypocretin neurons (PD: 20 276 (13 821-31229); controls: 36 842 (32 546-50 938); P = 0.016); (ii) the hypocretin-I concentration in post-mortem ventricular CSF (PD: 365.5 pg/ml (328.0-448.3); controls: 483.5 (433.5-512.3); P = 0.012) and (iii) the hypocretin-I concentrations in prefrontal cortex (PD: 389.6 pg/g (249.2-652.2); controls: 676.6 (467 5-883.9); P = 0.043). Hypocretin neurotransmission is affected in PD. The hypocretin- I concentration in the prefrontall cortex was almost 40% lower in PD patients, while ventricular CSF levels were almost 25% reduced. The total number of hypocretin neurons was almost half compared to controls.