Bazzett T J, Falik R C, Becker J B, Albin R L
Department of Neurology, University of Michigan, Ann Arbor 48104-1687, USA.
Exp Neurol. 1995 Aug;134(2):244-52. doi: 10.1006/exnr.1995.1054.
Adult rats received chronic dialytic delivery devices that exposed the striatum to a 100 mM, 400 mM, or 4 M solution of the reversible succinate dehydrogenase inhibitor malonic acid (MA). Three weeks of exposure to 100 or 400 mM MA produced no significant reduction in striatal cytochrome oxidase staining, whereas striata chronically exposed to 1 and 4 M MA showed a significant and dose-related reduction in cytochrome oxidase staining. In striata exposed to 1 M MA, analysis of regions radial to the necrotic core revealed significant reduction of nissl cell staining with relative sparing of NADPH-diaphorase-containing neurons. Although 100 and 400 mM MA failed to produce lesions, both of these concentrations significantly decreased the number of striatal calbindin (CALB) immunoreactive perikarya. The reduction in CALB immunoreactivity was partly reversed in animals allowed to survive 4 weeks after cessation of exposure to 400 mM MA. These results indicate that, like striatal lesions produced by quinolinic acid, lesions produced by chronic exposure to MA possess a Huntington's disease-like pattern of selective neurodegeneration. In addition, exposure to subthreshold MA concentrations (100 and 400 mM) produce widespread transient changes in striatal CALB that may be associated with a premorbid state of neuronal dysfunction.
成年大鼠接受了慢性透析给药装置，该装置使纹状体暴露于可逆性琥珀酸脱氢酶抑制剂丙二酸（MA）的100 mM、400 mM或4 M溶液中。暴露于100或400 mM MA三周后，纹状体细胞色素氧化酶染色没有显著减少，而长期暴露于1 M和4 M MA的纹状体显示细胞色素氧化酶染色显著且呈剂量相关减少。在暴露于1 M MA的纹状体中，对坏死核心径向区域的分析显示尼氏细胞染色显著减少，而含NADPH-黄递酶的神经元相对保留。虽然100和400 mM MA未能产生损伤，但这两种浓度均显著减少了纹状体钙结合蛋白（CALB）免疫反应阳性的核周体数量。在停止暴露于400 mM MA后存活4周的动物中，CALB免疫反应性的降低部分得到逆转。这些结果表明，与喹啉酸引起的纹状体损伤一样，慢性暴露于MA引起的损伤具有亨廷顿病样的选择性神经退行性变模式。此外，暴露于亚阈值MA浓度（100和400 mM）会使纹状体CALB产生广泛的短暂变化，这可能与神经元功能障碍的病前状态有关。
