Jordan Wolfgang, Tumani Hayrettin, Cohrs Stefan, Rodenbeck Andrea, Rüther Eckart, Bechthold Jens, Mayer Geert
Dept. of Psychiatry and Psychotherapy, Georg-August-University of Göttingen, von Sieboldstr. 5, 37075 Göttingen, Germany.
J Neurol. 2005 Nov;252(11):1372-8. doi: 10.1007/s00415-005-0870-4. Epub 2005 Jun 21.
Alterations in the prostaglandin-D-system have been found in animal sleep experiments and disorders that present with hypersomnia or sleep disturbances. The recently demonstrated involvement of the leptomeningeal lipocalin-type prostaglandin-Dsynthase (L-PGDS) (beta-trace) in human physiological sleep encouraged us to investigate its role in the pathophysiology of narcolepsy.
In a pilot study, serum LPGDS and melatonin concentrations were assessed in 14 narcoleptic patients during undisturbed sleep and total sleep deprivation, compared with those from 14 healthy controls during undisturbed sleep. Excessive daytime sleepiness was measured by a standardized questionnaire (Epworth sleepiness scale, ESS).
In narcoleptic patients, markedly increased baseline L-PGDS levels were significantly correlated with the ESS score, but not with the degree of cataplexy. Serum L-PGDS concentrations in patients as well as in controls followed a time-dependent fluctuation with evening increases, highest values during the night and in the morning. Compared with controls, patients exhibited significant/increased amplitude of circulating L-PGDS without any suppression by total sleep deprivation.
These findings indicate that the prostaglandin-D-system contributes to the pathophysiology of narcolepsy, e. g. the regulation of excessive daytime sleepiness. Since it has been suggested that L-PGDS is also involved in neurodegenerative disorders, there may be a more specific role of the prostaglandin- D-system in narcoleptic aetiogenesis. Moreover, its linkage with the immune system as well as with human sleep regulation offers a direct access for investigating both systems.
在动物睡眠实验以及伴有发作性睡病或睡眠障碍的病症中，已发现前列腺素-D系统存在改变。最近证实，软脑膜脂质运载蛋白型前列腺素-D合成酶（L-PGDS）（β-微量蛋白）参与人类生理性睡眠，这促使我们研究其在发作性睡病病理生理学中的作用。
在一项初步研究中，对14例发作性睡病患者在未受干扰睡眠和完全睡眠剥夺期间的血清LPGDS和褪黑素浓度进行了评估，并与14名健康对照者在未受干扰睡眠期间的相应指标进行比较。采用标准化问卷（爱泼华嗜睡量表，ESS）测量日间过度嗜睡情况。
在发作性睡病患者中，基线L-PGDS水平显著升高，且与ESS评分显著相关，但与猝倒程度无关。患者及对照者的血清L-PGDS浓度均呈现随时间的波动，夜间升高，在夜间和早晨达到最高值。与对照者相比，患者循环L-PGDS的振幅显著增加/升高，且完全睡眠剥夺并未对其产生任何抑制作用。
这些发现表明，前列腺素-D系统参与发作性睡病的病理生理学过程，例如对日间过度嗜睡的调节。由于有人提出L-PGDS也参与神经退行性疾病，前列腺素-D系统在发作性睡病病因学中可能具有更特殊的作用。此外，它与免疫系统以及人类睡眠调节的联系为研究这两个系统提供了直接途径。
