A pilot study assessing sphingolipids and glycolipids dysmetabolism in idiopathic normal pressure hydrocephalus
A pilot study assessing sphingolipids and glycolipids dysmetabolism in idiopathic normal pressure hydrocephalus
复制标题
DOI：
10.1016/j.bbrc.2022.11.091
复制
发表时间：
2022-12-05
影响因子：
3.1
通讯作者：
Hoshinaga, Kiyotaka
中科院分区：
文献类型：
--
作者：
Mutoh, Tatsuro;Niimi, Yoshiki;Hoshinaga, Kiyotaka
特发性正常压力脑积水通常表现出三联征，包括步态障碍、尿失禁和伴有脑室扩大的痴呆。目前，其发病机制仍有待完全阐明。为了更好地理解这一顺序，我们检查了患者脑脊液（CSF）中是否存在作为大脑中主要脂质成分的鞘脂代谢障碍。在这里，我们通过电喷雾电离串联质谱法测量了 19 名连续特发性正常压力脑积水患者、49 名帕金森病患者和 17 名神经系统正常对照者的脑脊液中的各种鞘脂，包括神经酰胺、鞘磷脂和糖脂。数据显示，所有半乳糖神经酰胺亚种水平均出现显着且特异性的降低。特发性正常压力脑积水患者与其他组相比，神经酰胺和鞘磷脂水平以及其他中性糖脂（例如葡萄糖神经酰胺和乳糖神经酰胺）在两种疾病状态下相似。性别和年龄的多元回归分析未显示与半乳糖神经酰胺水平存在任何相关性。我们还检查了 iNPH 患者的 MMSE 评分是否与鞘脂水平相关。在 iNPH 患者中，鞘磷脂的特定亚种 (d18:1/18:0) 仅与 MMSE 评分呈现统计学上显着的负相关性 (p = 0.0473，R =-0.4604)，但与其他鞘脂没有相关性。这些数据强烈表明，特发性正常压脑积水患者中富含髓磷脂的半乳糖神经酰胺代谢严重受损，可能作为该疾病生物标志物的基础。(c) 2022 Elsevier Inc. 保留所有权利。
Idiopathic normal pressure hydrocephalus usually exhibits triad of symptoms including gait disturbance, urinary incontinence, and dementia with ventriculomegaly. Currently, its pathogenesis remains to be fully elucidated.To provide a better understanding of this order, we examined whether dysmetabolism of sphingolipids as major lipid components in the brain present in cerebrospinal fluid (CSF) of the patients. Here, we measured various sphingolipidsincluding ceramide and sphingomyelin and glycolipids by electrospray ionization-tandem mass spectrometry in the cerebrospinal fluid of 19 consecutive idiopathic normal pressure hydrocephalus patients, 49 Parkinson's disease patients, and 17 neurologically normal controls.The data showed that there was a significant and specific reduction of all galactosylceramide sub-species levels in idiopathic normal pressure hydrocephalus patients compared with other groups, whereas ceramide and sphingomyelin levels as well as other neutral glycolipids such as glucosylcer-amide and lactosylceramide were similar in both disease states. Multiple regression analysis of sex and age did not show any correlation with galactosylceramide levels. We also examined whether MMSE scores are correlated with sphingolipid levels in iNPH patients. A specific subspecies of sphingomyelin (d18:1/18:0) only exhibited a statistically significant negative correlation (p = 0.0473, R =-0.4604) with MMSE scores but no other sphingolipids in iNPH patients. These data strongly suggest that myelin-rich galactosylceramide metabolism is severely impaired in idiopathic normal pressure hydrocephalus pa-tients and might serve as the basis of biomarker for this disorder.(c) 2022 Elsevier Inc. All rights reserved.