Flanagan E M, Erickson J B, Viveros O H, Chang S Y, Reinhard J F
Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
J Neurochem. 1995 Mar;64(3):1192-6. doi: 10.1046/j.1471-4159.1995.64031192.x.
Experimental allergic encephalomyelitis (EAE) is an autoimmune, animal model of multiple sclerosis (MS) in which demyelination and paralysis are evident. Quinolinic acid (QUIN) is a neurotoxin and endogenous N-methyl-D-aspartate receptor agonist formed from tryptophan. The role of neurotoxins in general and QUIN in particular in EAE or MS is unknown. Lewis rats inoculated with myelin basic protein developed signs of EAE by day 12, were killed, and their tissues assayed for QUIN by gas chromatography with mass spectrometry. QUIN levels were significantly elevated in the more caudal regions of the spinal cords of animals with EAE. Brain, serum, and liver levels of QUIN were not altered. In a similar manner, QUIN in mylin basic protein-injected, asymptomatic animals was not different from control animals. The time course for QUIN was similar to the neurological signs of the disorder; however, the initial elevation in QUIN occurred before the appearance of behavioral signs. Last, treatment with the glucocorticoid dexamethasone prevented both the signs of EAE and the elevation in spinal cord QUIN. It is not known whether QUIN contributes to the paralysis in EAE. However, if QUIN is pathogenic in EAE this finding could have therapeutic implications for MS.
实验性自身免疫性脑脊髓炎（EAE）是一种多发性硬化症（MS）的自身免疫性动物模型，其中脱髓鞘和麻痹现象明显。喹啉酸（QUIN）是一种神经毒素，也是由色氨酸形成的内源性N-甲基-D-天冬氨酸受体激动剂。一般来说，神经毒素尤其是QUIN在EAE或MS中的作用尚不清楚。接种髓鞘碱性蛋白的Lewis大鼠在第12天出现EAE症状，随后被处死，其组织通过气相色谱-质谱联用仪检测QUIN。患有EAE的动物脊髓尾端区域的QUIN水平显著升高。大脑、血清和肝脏中的QUIN水平没有变化。同样，注射髓鞘碱性蛋白的无症状动物体内的QUIN与对照动物没有差异。QUIN的时间进程与该疾病的神经学症状相似；然而，QUIN的最初升高发生在行为症状出现之前。最后，用糖皮质激素地塞米松治疗可预防EAE症状和脊髓QUIN水平的升高。尚不清楚QUIN是否导致EAE中的麻痹。然而，如果QUIN在EAE中具有致病性，这一发现可能对MS具有治疗意义。
