Browne Susan E, Yang Lichuan, DiMauro Jon-Paul, Fuller Sara W, Licata Stephanie C, Beal M Flint
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 E. 68th Street, A-502, New York, NY 10021, USA.
Neurobiol Dis. 2006 Jun;22(3):599-610. doi: 10.1016/j.nbd.2006.01.001. Epub 2006 Apr 17.
Multiple cell death pathways are implicated in the etiology of amyotrophic lateral sclerosis (ALS), but the cause of the characteristic motor neuron degeneration remains unknown. To determine whether CNS metabolic defects are critical for ALS pathogenesis, we examined the temporal evolution of energetic defects in the G93A SOD1 mouse model of familial ALS. [14C]-2-deoxyglucose in vivo autoradiography in G93A mice showed that glucose utilization is impaired in components of the corticospinal and bulbospinal motor tracts prior to either pathologic or bioenergetic changes in the spinal cord. This was accompanied by significant depletions in cortical ATP content in presymptomatic mice, which was partially ameliorated by creatine administration. Findings suggest that bioenergetic defects are involved in the initial stages of mSOD1-induced toxicity in G93A mice and imply that the selective dysfunction and degeneration of spinal cord motor neurons in this model may be secondary to dysfunction within cerebral motor pathways.
多种细胞死亡途径与肌萎缩侧索硬化症（ALS）的病因有关，但特征性运动神经元变性的原因仍然未知。为了确定中枢神经系统代谢缺陷对ALS发病机制是否至关重要，我们研究了家族性ALS的G93A SOD1小鼠模型中能量缺陷的时间演变。G93A小鼠体内的[14C]-2-脱氧葡萄糖放射自显影显示，在脊髓发生病理或生物能量变化之前，皮质脊髓和延髓脊髓运动束的组成部分中葡萄糖利用受损。这伴随着症状前小鼠皮质ATP含量的显著消耗，补充肌酸可部分改善这种情况。研究结果表明，生物能量缺陷参与了G93A小鼠中mSOD1诱导毒性的初始阶段，并暗示该模型中脊髓运动神经元的选择性功能障碍和变性可能继发于脑运动通路内的功能障碍。
