Bazzett T J, Becker J B, Falik R C, Albin R L
Department of Neurology, University of Michigan, Ann Arbor 48104-1687.
Neuroscience. 1994 Jun;60(4):837-41. doi: 10.1016/0306-4522(94)90266-6.
We recently reported the use of a chronic dialytic delivery system for intrastriatal administration of quinolinic acid in the rat. This system produces neurodegeneration with some characteristics similar to post mortem brain tissue from Huntington's disease patients, including reduced cytochrome oxidase staining, a decreased number of Nissl-stained neurons, and relative sparing of striatal NADPH-diaphorase containing neurons. The present findings show that chronic dialytic delivery of quinolinic acid also produces a Huntington's disease-like pattern of reduced calbindin and parvalbumin perikaryal immunoreactivity that is reversed in rats allowed four to eight weeks' recovery after cessation of quinolinic acid. Furthermore, cytochrome oxidase staining and the number of Nissl-stained cells were unchanged in the region of transient calbindin and parvalbumin immunoreactive perikaryal staining alterations. These results suggest that changes in calbindin and parvalbumin perikaryal immunoreactivity provide a relatively sensitive measure of quinolinic acid induced neurotoxicity. The reversible nature of reduced perikaryal immunoreactivity suggests a premorbid state of neurotoxicity, possibly marked by cellular redistribution of calbindin and parvalbumin.
我们最近报道了在大鼠中使用慢性透析给药系统向纹状体内注射喹啉酸。该系统会引发神经退行性变，其某些特征与亨廷顿病患者的死后脑组织相似，包括细胞色素氧化酶染色减少、尼氏染色神经元数量减少，以及纹状体内含烟酰胺腺嘌呤二核苷酸磷酸黄递酶（NADPH-d）的神经元相对保留。目前的研究结果表明，慢性透析给药喹啉酸还会产生一种类似亨廷顿病的模式，即钙结合蛋白和小白蛋白的核周免疫反应性降低，在停止注射喹啉酸后经过四至八周恢复的大鼠中这种情况会逆转。此外，在钙结合蛋白和小白蛋白免疫反应性核周染色短暂改变的区域，细胞色素氧化酶染色和尼氏染色细胞数量没有变化。这些结果表明，钙结合蛋白和小白蛋白核周免疫反应性的变化为喹啉酸诱导的神经毒性提供了一个相对敏感的指标。核周免疫反应性降低的可逆性表明存在神经毒性的病前状态，可能以钙结合蛋白和小白蛋白的细胞重新分布为特征。
