Gressens P, Baes M, Leroux P, Lombet A, Van Veldhoven P, Janssen A, Vamecq J, Marret S, Evrard P
INSERM E 9935 and Service de Neurologie Pédiatrique, Hôpital Robert-Debré, Paris, France.
Ann Neurol. 2000 Sep;48(3):336-43.
Disorders of neuronal migration in cerebral cortex are associated with neurological impairments, including mental retardation and epilepsy. Their causes and pathophysiology remain largely unknown, however. In patients with Zellweger disease, a lethal panperoxisomal disorder, and in mice lacking the Pxr1 import receptor for peroxisomal matrix proteins, the absence of peroxisomes leads to abnormal neuronal migration. Analysis of Pxr1-/- mice revealed that the migration defect was caused by altered N-methyl-D-aspartate (NMDA) glutamate receptor-mediated calcium mobilization. This NMDA receptor dysfunction was linked to a deficit in platelet-activating factor, a phenomenon related to peroxisome impairment. These findings confirm NMDA receptor involvement in neuronal migration and suggest a link between peroxisome metabolism and NMDA receptor efficacy.
大脑皮层神经元迁移障碍与神经功能损伤有关，包括智力迟钝和癫痫。然而，其病因和病理生理学在很大程度上仍不清楚。在患有致命性全过氧化物酶体疾病的泽尔韦格氏病患者以及缺乏过氧化物酶体基质蛋白的Pxr1导入受体的小鼠中，过氧化物酶体的缺失会导致神经元迁移异常。对Pxr1基因敲除小鼠的分析表明，迁移缺陷是由N-甲基-D-天冬氨酸（NMDA）谷氨酸受体介导的钙动员改变引起的。这种NMDA受体功能障碍与血小板活化因子缺乏有关，这一现象与过氧化物酶体损伤有关。这些发现证实了NMDA受体参与神经元迁移，并提示过氧化物酶体代谢与NMDA受体效能之间存在联系。
