Nishino S, Ripley B, Overeem S, Nevsimalova S, Lammers G J, Vankova J, Okun M, Rogers W, Brooks S, Mignot E
Stanford University Center for Narcolepsy, Palo Alto, CA 94304, USA.
Ann Neurol. 2001 Sep;50(3):381-8. doi: 10.1002/ana.1130.
Hypocretins (orexins) are hypothalamic neuropeptides involved in sleep and energy homeostasis. Hypocretin mutations produce narcolepsy in animal models. In humans, narcolepsy is rarely due to hypocretin mutations, but this system is deficient in the cerebrospinal fluid (CSF) and brain of a small number of patients. A recent study also indicates increased body mass index (BMI) in narcolepsy. The sensitivity of low CSF hypocretin was examined in 38 successive narcolepsy-cataplexy cases [36 human leukocyte antigen (HLA)-DQB1*0602-positive] and 34 matched controls (15 controls and 19 neurological patients). BMI and CSF leptin levels were also measured. Hypocretin-1 was measurable (169 to 376 pg/ml) in all controls. Levels were unaffected by freezing/thawing or prolonged storage and did not display any concentration gradient. Hypocretin-1 was dramatically decreased (<100 pg/ml) in 32 of 38 patients (all HLA-positive). Four patients had normal levels (2 HLA-negative). Two HLA-positive patients had high levels (609 and 637 pg/ml). CSF leptin and adjusted BMI were significantly higher in patients versus controls. We conclude that the hypocretin ligand is deficient in most cases of human narcolepsy, providing possible diagnostic applications. Increased BMI and leptin indicate altered energy homeostasis. Sleep and energy metabolism are likely to be functionally connected through the hypocretin system.
下丘脑泌素（食欲素）是参与睡眠和能量稳态的下丘脑神经肽。下丘脑泌素突变在动物模型中会导致发作性睡病。在人类中，发作性睡病很少由下丘脑泌素突变引起，但在少数患者的脑脊液（CSF）和大脑中该系统存在缺陷。最近的一项研究还表明发作性睡病患者的体重指数（BMI）增加。对38例连续的发作性睡病 - 猝倒症患者[36例人类白细胞抗原（HLA） - DQB1*0602阳性]和34例匹配对照（15例对照和19例神经科患者）进行了低脑脊液下丘脑泌素敏感性检查。还测量了BMI和脑脊液瘦素水平。所有对照中下丘脑泌素 - 1均可测量（169至376 pg/ml）。其水平不受冻融或长期储存的影响，也未显示任何浓度梯度。38例患者中有32例（均为HLA阳性）下丘脑泌素 - 1显著降低（<100 pg/ml）。4例患者水平正常（2例HLA阴性）。2例HLA阳性患者水平较高（609和637 pg/ml）。患者的脑脊液瘦素和校正后的BMI显著高于对照。我们得出结论，在大多数人类发作性睡病病例中下丘脑泌素配体缺乏，这为诊断应用提供了可能。BMI和瘦素增加表明能量稳态改变。睡眠和能量代谢可能通过下丘脑泌素系统在功能上相互联系。
