Abstract

D-serine is an endogenous co-agonist with glutamate for activation of the N-methyl-D-aspartate receptor (NMDAR). D-serine exacerbates neuronal death and is elevated in the spinal cord from patients with sporadic/familial ALS. The present study was undertaken to examine whether plasma levels of D-serine of patients with ALS are different from those of healthy controls. Levels of D-serine in plasma (30 patients and 30 controls) were measured by high-performance liquid chromatography mass spectrometry. Plasma levels of D-serine in ALS patients (mean 39.27 ± 28.61 ng/ml) were significantly higher (p = 0.0293) than those of healthy control subjects (mean 21.07 ± 14.03 ng/ml) as well as previously reported values for healthy controls; ∼43% of patients had plasma D-serine levels that were 2 to 4-folds higher than those of controls. There was no association of plasma D-serine levels with disability, the duration of disease or with the age of subjects. In conclusion, we show that D-serine levels are elevated in the plasma of some ALS patients. Since D-serine serves as a co-agonist/activator of NMDAR, increases in D-serine could have a direct influence on glutamatergic neurotransmission and potentially contribute to excitotoxicity in some ALS patients.

摘要

D-丝氨酸是一种与谷氨酸一起激活N-甲基-D-天冬氨酸受体 (NMDAR)的内源性共激动剂。D-丝氨酸会加剧神经元死亡，并在散发性/家族性 ALS 患者的脊髓中升高。本研究旨在检查 ALS 患者的血浆 D-丝氨酸水平是否与健康对照者不同。通过高效液相色谱质谱法测量血浆（30 名患者和 30 名对照者）中 D-丝氨酸的水平。ALS 患者的血浆 D-丝氨酸水平（平均 39.27 ± 28.61 ng/ml）显着更高（p = 0.0293) 比健康对照受试者（平均 21.07 ± 14.03 ng/ml）以及先前报告的健康对照值；约 43% 的患者血浆 D-丝氨酸水平比对照组高 2 至 4 倍。血浆 D-丝氨酸水平与残疾、疾病持续时间或受试者年龄无关。总之，我们表明一些 ALS 患者的血浆中 D-丝氨酸水平升高。由于 D-丝氨酸作为 NMDAR 的共激动剂/激活剂，D-丝氨酸的增加可能对谷氨酸能神经传递有直接影响，并可能导致某些 ALS 患者出现兴奋性毒性。