Zhang X, Chen S, Li L, Wang Q, Le W
Insitute of Neurology, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai, China.
J Neurol Sci. 2010 Jun 15;293(1-2):102-5. doi: 10.1016/j.jns.2010.02.024. Epub 2010 Mar 23.
Several studies have reported that homocysteine (Hcy) is associated with amyotrophic lateral sclerosis (ALS), a neurodegenerative disease without special biomarkers for early diagnosis. Here, we examined the levels of Hcy, folic acid and its metabolic molecule 5-methyltetrahydrofolate (5-MTHF) in SOD1(G93A) transgenic mouse model of ALS in an attempt to determine whether the change in those molecules can be used as potential biomarkers for the disease.
According to the disease progression, SOD1(G93A) transgenic mice were divided into early stage group (30d); pre-symptom group (60d); symptom group (90d) and terminal stage group (120d). LC-MS/MS was used to measure the level of Hcy, folic acid and 5-MTHF in the plasma, spinal cord and cortex of the ALS transgenic SOD1(G93A) mice at different disease stages. Nissl staining was used to detect the motor neurons survival in the anterior horn of the spinal cord of the SOD1(G93A) mice.
In this study, we demonstrated that the level of 5-MTHF is significantly decreased in the plasma, spinal cord and cortex at the early stages of pre-symptomatic ALS transgenic SOD1(G93A) mice while folic acid is decreased at the middle to late stages of the disease. Furthermore, we found that the level of Hcy is markedly elevated after the motor symptoms appeared in the ALS mice.
Our study suggests that decreased 5-MTHF level may be a potential biomarker for the early stage of the disease in the ALS mice, which may warrant further validating study of 5-MTHF level in ALS patients.
多项研究报告称，同型半胱氨酸（Hcy）与肌萎缩侧索硬化症（ALS）相关，ALS是一种没有用于早期诊断的特殊生物标志物的神经退行性疾病。在此，我们检测了ALS的SOD1（G93A）转基因小鼠模型中Hcy、叶酸及其代谢分子5-甲基四氢叶酸（5-MTHF）的水平，以确定这些分子的变化是否可作为该疾病的潜在生物标志物。
根据疾病进展，将SOD1（G93A）转基因小鼠分为早期组（30天）；症状前期组（60天）；症状组（90天）和终末期组（120天）。采用液相色谱-串联质谱法（LC-MS/MS）测量不同疾病阶段的ALS转基因SOD1（G93A）小鼠血浆、脊髓和皮质中Hcy、叶酸和5-MTHF的水平。采用尼氏染色法检测SOD1（G93A）小鼠脊髓前角运动神经元的存活情况。
在本研究中，我们证明，在症状前期ALS转基因SOD1（G93A）小鼠的早期，血浆、脊髓和皮质中的5-MTHF水平显著降低，而叶酸在疾病的中晚期降低。此外，我们发现ALS小鼠出现运动症状后，Hcy水平显著升高。
我们的研究表明，5-MTHF水平降低可能是ALS小鼠疾病早期的潜在生物标志物，这可能需要对ALS患者的5-MTHF水平进行进一步的验证研究。
