Niimi Yoshiki, Ueda Akihiro, Akiyama Hisako, Shiroki Ryoichi, Greimel Peter, Hirabayashi Yoshio, Hoshinaga Kiyotaka, Mutoh Tatsuro
Department of Neurology, Fujita Health University Hospital, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
RIKEN Center for Brain Science, Wako, Saitama, Japan.
Mol Cell Biochem. 2025 Jul 22. doi: 10.1007/s11010-025-05334-8.
Although glycosphingolipids (GSLs) and sterol metabolites are known to be involved in many diseases, including neurodegenerative disorders, the quantification of these molecules in humans has been scarcely investigated. Similarly, the effects of age, sex, and statin use have not been sufficiently investigated or reported in the literature. In this study, we measured the levels of human cerebrospinal fluid (CSF) GSLs of various fatty acid acyl chain lengths and sterol metabolites using hydrophilic interaction liquid chromatography and electrospray tandem mass spectrometry in a neurologically normal population. We successfully quantified the presence of glucosylated cholesterol, galactosylated cholesterol, glucosylated sitosterol, glucosylceramide (GlcCer), galactosylceramide, lactosylceramide (LacCer), and galabiosylceramide (Gb2). There were no statistically significant differences in CSF concentrations of these lipids between males and females. We also found no correlation between CSF concentration and age or statin dose, except for GlcCer d18:1-C23:1. Significant positive correlations with age were shown only in males. Our results indicate that, in future studies, age and sex should be taken into consideration when comparing CSF GSL levels in patients with neurological disorders with those in neurologically normal control subjects.
尽管已知糖鞘脂（GSLs）和甾醇代谢产物与包括神经退行性疾病在内的多种疾病有关，但对这些分子在人体中的定量研究却很少。同样，年龄、性别和他汀类药物使用的影响在文献中也没有得到充分研究或报道。在本研究中，我们使用亲水相互作用液相色谱和电喷雾串联质谱法，在神经功能正常的人群中测量了各种脂肪酸酰基链长度的人脑脊液（CSF）GSLs和甾醇代谢产物的水平。我们成功地定量了葡萄糖基化胆固醇、半乳糖基化胆固醇、葡萄糖基化谷甾醇、葡萄糖神经酰胺（GlcCer）、半乳糖神经酰胺、乳糖神经酰胺（LacCer）和二半乳糖神经酰胺（Gb2）的存在。这些脂质在男性和女性脑脊液中的浓度没有统计学上的显著差异。我们还发现脑脊液浓度与年龄或他汀类药物剂量之间没有相关性，除了GlcCer d18:1-C23:1。仅在男性中显示出与年龄的显著正相关。我们的结果表明，在未来的研究中，在比较神经疾病患者与神经功能正常对照受试者的脑脊液GSL水平时，应考虑年龄和性别因素。
