Brouillet E, Jenkins B G, Hyman B T, Ferrante R J, Kowall N W, Srivastava R, Roy D S, Rosen B R, Beal M F
Department of Pathology, Massachusetts General Hospital, Boston 02114.
J Neurochem. 1993 Jan;60(1):356-9. doi: 10.1111/j.1471-4159.1993.tb05859.x.
The mechanisms of delayed onset and cell death in Huntington's disease (HD) are unknown. One possibility is that a genetic defect in energy metabolism may result in slow excitotoxic neuronal death. Therefore, we examined the effects of age on striatal lesions produced by local administration of the mitochondrial toxin 3-nitropropionic acid in rats. In vivo chemical shift magnetic resonance imaging showed marked increases in striatal lactate concentrations that significantly correlated with increasing age. Histologic and neurochemical studies showed a striking age dependence of the lesions, with 4- and 12-month-old animals being much more susceptible than 1-month-old animals. Continuous systemic administration of low doses of 3-nitropropionic acid for 1 month resulted in striatal lesions showing growth-related changes in dendrites of striatal spiny neurons using the Golgi technique. These results show that a known mitochondrial toxin can produce selective axon-sparing striatal lesions showing both the age dependence and striatal spiny neuron dendritic changes that characterize HD.
亨廷顿舞蹈病（HD）延迟发作和细胞死亡的机制尚不清楚。一种可能性是能量代谢中的基因缺陷可能导致兴奋性毒性神经元缓慢死亡。因此，我们研究了年龄对大鼠局部给予线粒体毒素3-硝基丙酸所产生的纹状体损伤的影响。体内化学位移磁共振成像显示纹状体乳酸浓度显著增加，且与年龄增长显著相关。组织学和神经化学研究显示损伤具有明显的年龄依赖性，4个月和12个月大的动物比1个月大的动物更易受影响。连续1个月低剂量全身给予3-硝基丙酸导致纹状体损伤，使用高尔基技术显示纹状体棘状神经元树突出现与生长相关的变化。这些结果表明，一种已知的线粒体毒素可产生选择性保留轴突的纹状体损伤，表现出HD所特有的年龄依赖性和纹状体棘状神经元树突变化。
