Quantifying Beta-Galactosylceramide Kinetics in Cerebrospinal Fluid of Healthy Subjects Using Deuterium Labeling
Quantifying Beta-Galactosylceramide Kinetics in Cerebrospinal Fluid of Healthy Subjects Using Deuterium Labeling
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DOI：
10.1111/cts.12424
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发表时间：
2016-12-01
影响因子：
3.9
通讯作者：
Groeneveld, G. J.
中科院分区：
文献类型：
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作者：
Kanhai, K. M. S.;Goulooze, S. C.;Groeneveld, G. J.
促进髓磷脂合成的治疗可能会促进脱髓鞘疾病（例如多发性硬化症）的恢复。然而，不存在量化髓鞘形成的合适方法。半乳糖神经酰胺（髓鞘质成分）的周转率可以指示小鼠的髓鞘形成，但其在人类中的周转率尚未确定。在此，六名健康受试者连续 70 天每天消耗 120 mL 70% D2O 以标记半乳糖神经酰胺。然后，我们使用质谱法和区室模型来量化脑脊液中半乳糖神经酰胺的周转率。体内水的氘最大富集范围为 1.5-3.9%，而半乳糖神经酰胺的最大富集范围则低得多：0.05-0.14%。这表明周转率较慢，模型估计的半乳糖神经酰胺周转率为 0.00168 天(-1)，对应的半衰期为 413 天，这证实了这一点。需要对多发性硬化症患者进行更多研究，以调查半乳糖神经酰胺周转率是否可以用作髓鞘再生治疗临床试验的结果指标。
Therapeutics promoting myelin synthesis may enhance recovery in demyelinating diseases, such as multiple sclerosis. However, no suitable method exists to quantify myelination. The turnover of galactosylceramide ( myelin component) is indicative of myelination in mice, but its turnover has not been determined in humans. Here, six healthy subjects consumed 120 mL 70% D2O daily for 70 days to label galactosylceramide. We then used mass spectrometry and compartmental modeling to quantify the turnover rate of galactosylceramide in cerebrospinal fluid. Maximum deuterium enrichment of body water ranged from 1.5-3.9%, whereas that of galactosylceramide was much lower: 0.05-0.14%. This suggests a slow turnover rate, which was confirmed by the model-estimated galactosylceramide turnover rate of 0.00168 day(-1), which corresponds to a half-life of 413 days. Additional studies in patients with multiple sclerosis are needed to investigate whether galactosylceramide turnover could be used as an outcome measure in clinical trials with remyelination therapies.