Sako Wataru, Abe Takashi, Izumi Yuishin, Harada Masafumi, Kaji Ryuji
Department of Clinical Neuroscience, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan.
Department of Radiology, Institute of Health Biosciences, Tokushima University Graduate School, Tokushima, Japan.
J Clin Neurosci. 2016 May;27:110-3. doi: 10.1016/j.jocn.2015.08.044. Epub 2016 Jan 4.
Glutamate (Glu)-induced excitotoxicity has been implicated in the neuronal loss of amyotrophic lateral sclerosis. To test the hypothesis that Glu in the primary motor cortex contributes to disease severity and/or duration, the Glu level was investigated using MR spectroscopy. Seventeen patients with amyotrophic lateral sclerosis were diagnosed according to the El Escorial criteria for suspected, possible, probable or definite amyotrophic lateral sclerosis, and enrolled in this cross-sectional study. We measured metabolite concentrations, including N-acetyl aspartate (NAA), creatine, choline, inositol, Glu and glutamine, and performed partial correlation between each metabolite concentration or NAA/Glu ratio and disease severity or duration using age as a covariate. Considering our hypothesis that Glu is associated with neuronal cell death in amyotrophic lateral sclerosis, we investigated the ratio of NAA to Glu, and found a significant correlation between NAA/Glu and disease duration (r=-0.574, p=0.02). The "suspected" amyotrophic lateral sclerosis patients showed the same tendency as possible, probable and definite amyotrophic lateral sclerosis patients in regard to correlation of NAA/Glu ratio with disease duration. The other metabolites showed no significant correlation. Our findings suggested that glutamatergic neurons are less vulnerable compared to other neurons and this may be because inhibitory receptors are mainly located presynaptically, which supports the notion of Glu-induced excitotoxicity.
谷氨酸（Glu）诱导的兴奋性毒性与肌萎缩侧索硬化症的神经元丢失有关。为了验证初级运动皮层中的Glu会导致疾病严重程度和/或病程的假设，我们使用磁共振波谱对Glu水平进行了研究。17例肌萎缩侧索硬化症患者根据El Escorial标准被诊断为疑似、可能、很可能或确诊的肌萎缩侧索硬化症，并纳入了这项横断面研究。我们测量了包括N-乙酰天门冬氨酸（NAA）、肌酸、胆碱、肌醇、Glu和谷氨酰胺在内的代谢物浓度，并以年龄作为协变量，对每种代谢物浓度或NAA/Glu比值与疾病严重程度或病程进行了偏相关分析。考虑到我们关于Glu与肌萎缩侧索硬化症中神经元细胞死亡相关的假设，我们研究了NAA与Glu的比值，发现NAA/Glu与病程之间存在显著相关性（r = -0.574，p = 0.02）。在NAA/Glu比值与病程的相关性方面，“疑似”肌萎缩侧索硬化症患者与可能、很可能和确诊的肌萎缩侧索硬化症患者表现出相同的趋势。其他代谢物未显示出显著相关性。我们的研究结果表明，与其他神经元相比，谷氨酸能神经元更不易受损，这可能是因为抑制性受体主要位于突触前，这支持了Glu诱导的兴奋性毒性的观点。
