Cruz-Sanchez F F, Cardozo A, Ambrosio S, Tolosa E, Mahy N
Neurological Tissue Bank, University of Barcelona, Hospital Clínico y Provincial, Spain.
Mol Chem Neuropathol. 1993 May-Jun;19(1-2):163-76. doi: 10.1007/BF03160176.
In order to compare the recovery capacity of the nigrostriatal system between adult and old mice, MPTP hydrochloride was administered to 48 BL/C57 male mice, which were sacrificed 24 h or 10 d after the second dose. The animals were divided into four groups, based on age (adult or old) and moment of sacrifice (24 h or 10 d). The detailed morphology of the neurons and the cellular processes of the substantia nigra pars compacta and the striatum were studied using the Golgi method. Immunostaining with a polyclonal glial fibrillary acidic protein antiserum using the peroxidase-antiperoxidase technique was performed to study the glial response. Striatal catecholamines were determined to correlate the biochemical data with the morphological changes. Significant neuronal changes of cellular processes were observed in substantia nigra pars compacta from all MPTP-treated mice, consisting of swelling and distortion of cellular bodies, discontinuous thickness, and nodulations of dendrites with baded aspect. Axons showing focal swelling and nodulations were also found in the neuropil of silver impregnated striata. Marked gliosis with reactive astrocytes in substantia nigra and striatum from all the old treated mice was found. Recovery was only observed in adult mice sacrificed 10 d after withdrawal. At this time, all the old MPTP-treated mice showed marked neuronal changes and a persistent marked gliosis. As expected, 24 h after the MPTP treatment, a marked depletion of dopamine and its metabolites was found in all the animals; at 10 d, the depletion was partially reversed in the adult group. These data correlate well with the observed morphological changes. Our results suggest that, in mice, deterioration of dendritic and axonal neuropil constitutes a significant causal factor of the MPTP neurotoxicity. These features are related to the age of the animals and the integrity of the plasticity phenomena, which appear to be altered in old mice.
为了比较成年小鼠和老年小鼠黑质纹状体系统的恢复能力，将盐酸MPTP注射给48只BL/C57雄性小鼠，在第二次给药后24小时或10天处死。根据年龄（成年或老年）和处死时间（24小时或10天）将动物分为四组。使用高尔基方法研究黑质致密部和纹状体神经元及细胞突起的详细形态。采用过氧化物酶-抗过氧化物酶技术，用多克隆胶质纤维酸性蛋白抗血清进行免疫染色，以研究胶质细胞反应。测定纹状体儿茶酚胺，将生化数据与形态学变化相关联。在所有经MPTP处理的小鼠的黑质致密部均观察到细胞突起的显著神经元变化，包括细胞体肿胀和变形、厚度不连续以及树突呈结节状且外观不佳。在银染纹状体的神经毡中也发现了显示局灶性肿胀和结节的轴突。在所有经处理的老年小鼠的黑质和纹状体中均发现有反应性星形胶质细胞的明显胶质增生。仅在停药后10天处死的成年小鼠中观察到恢复。此时，所有经MPTP处理的老年小鼠均表现出显著的神经元变化和持续的明显胶质增生。正如预期的那样，在MPTP处理后24小时，所有动物的多巴胺及其代谢产物均显著耗竭；在10天时，成年组的耗竭情况部分得到逆转。这些数据与观察到的形态学变化密切相关。我们的结果表明，在小鼠中，树突和轴突神经毡的退化是MPTP神经毒性的一个重要致病因素。这些特征与动物的年龄以及可塑性现象的完整性有关，而可塑性现象在老年小鼠中似乎发生了改变。
