Shaughnessy L W, Barone S, Mundy W R, Herr D W, Tilson H A
University of North Carolina, Chapel Hill 27599.
Brain Res. 1994 Feb 21;637(1-2):15-26. doi: 10.1016/0006-8993(94)91212-2.
Colchicine and ibotenic acid were compared for their ability to produce neurodegeneration and cognitive deficit after bilateral infusions into the nucleus basalis magnocellularis of male Long-Evans rats. Four weeks post-lesion, there was no difference in locomotor activity following infusion of either neurotoxicant or vehicle. In a passive avoidance task, both treated groups had significantly shorter step-through latencies compared with vehicle. Five weeks post-lesion, rats were killed for neurochemistry or histochemistry. Choline acetyltransferase (ChAT) activity in both the frontal and parietal cortex was significantly decreased (25-35%) in the colchicine- and ibotenic acid-infused rats when compared to control. There was no effect of either neurotoxicant on ChAT activity in the hippocampus or striatum. Both neurotoxicants produced damage in the general area of the ventromedial pallidum, although ibotenic acid infusion consistently produced a larger area of damage as assessed in Nissl-stained sections. Analysis of the number of ChAT-immunoreactive cells in the nucleus basalis magnocellularis (NBM) showed an average 60% cell loss following colchicine infusion and a 75% cell loss after ibotenic acid infusion. Area of glutamic acid decarboxylase (GAD) staining was significantly decreased in several regions surrounding the NBM for ibotenic acid (51% average decrease), and showed non-significant decreases (28%) following colchicine infusion. Colchicine infusion decreased dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum; ibotenic acid had no effect on brain catechol of indoleamine levels. The results indicate that although similar cholinergic hypofunction and behavioral deficits were achieved, several non-cholinergic differences between the neurotoxicants were detected.
将秋水仙碱和鹅膏蕈氨酸双侧注入雄性Long-Evans大鼠的基底大细胞核后，比较了它们产生神经退行性变和认知缺陷的能力。损伤后四周，注入任何一种神经毒素或赋形剂后，大鼠的运动活动没有差异。在被动回避任务中，与注入赋形剂的大鼠相比，两个治疗组的穿通潜伏期均显著缩短。损伤后五周，处死大鼠进行神经化学或组织化学分析。与对照组相比，注入秋水仙碱和鹅膏蕈氨酸的大鼠额叶和顶叶皮质中的胆碱乙酰转移酶（ChAT）活性显著降低（25%-35%）。两种神经毒素对海马体或纹状体中的ChAT活性均无影响。两种神经毒素均在腹内侧苍白球的大致区域造成损伤，不过，根据尼氏染色切片评估，注入鹅膏蕈氨酸后造成的损伤区域始终更大。对基底大细胞核（NBM）中ChAT免疫反应性细胞数量的分析显示，注入秋水仙碱后细胞平均损失60%，注入鹅膏蕈氨酸后细胞损失75%。鹅膏蕈氨酸注入后，NBM周围几个区域的谷氨酸脱羧酶（GAD）染色面积显著减少（平均减少51%），注入秋水仙碱后GAD染色面积减少不显著（28%）。注入秋水仙碱会降低纹状体中的多巴胺和3,4-二羟基苯乙酸（DOPAC）；鹅膏蕈氨酸对脑儿茶酚胺或吲哚胺水平没有影响。结果表明，尽管两种神经毒素导致了相似的胆碱能功能减退和行为缺陷，但也发现了它们之间一些非胆碱能方面的差异。
