Holley L A, Wiley R G, Lappi D A, Sarter M
Department of Psychology, Ohio State University, Columbus 43210.
Brain Res. 1994 Nov 14;663(2):277-86. doi: 10.1016/0006-8993(94)91274-2.
The immunotoxin 192 IgG-saporin has been hypothesized to selectively lesion cholinergic neurons that bear the low-affinity p75 nerve growth factor (NGF) receptor. To evaluate the usefulness of this toxin in studies intended to determine the functions of cholinergic afferents of cortical areas, relatively small concentrations and volumes of the immunotoxin (0.01-0.05 micrograms/0.5-1.0 microliters) were infused into cortical areas of one hemisphere of rats, while the vehicle was infused into homologous areas of the contralateral hemisphere. The effects of these infusions on the density of cortical acetylcholinesterase (AChE)-positive fibers and of normal fibers (as revealed by a reduced silver stain) were quantified. The infusion of the immunotoxin did not produce local gliosis in excess of the gliosis resulting from the infusion of vehicle. When compared with the frontoparietal cortex of the intact hemisphere, the number of cortical AChE-positive fibers was reduced by 36-39% and the density of the silver-stained fibers was decreased by 20-25%. While the loss of AChE-positive fibers and silver-stained fibers correlated significantly in layers V/VI, a linear regression analysis suggested that the magnitude of the loss of AChE-positive fibers was greater than would be predicted on the basis of the residual density of normal fibers. Thus, the data suggest that infusions of 192 IgG-saporin into the cortex did not result in the loss of non-cholinergic afferents. Intracortical infusions of relatively small concentrations and volumes of 192 IgG-saporin appear to provide a useful approach for the examination of the functions of cholinergic inputs to specific cortical regions.
免疫毒素192 IgG-皂草素被推测可选择性损伤携带低亲和力p75神经生长因子（NGF）受体的胆碱能神经元。为评估该毒素在旨在确定皮质区域胆碱能传入神经功能的研究中的效用，将相对低浓度和小体积的免疫毒素（0.01 - 0.05微克/0.5 - 1.0微升）注入大鼠一侧半球的皮质区域，而将赋形剂注入对侧半球的同源区域。对这些注入对皮质乙酰胆碱酯酶（AChE）阳性纤维密度和正常纤维（经还原银染色显示）密度的影响进行了量化。注入免疫毒素未产生超过赋形剂注入所致的局部胶质增生。与完整半球的额顶叶皮质相比，皮质AChE阳性纤维数量减少了36 - 39%，银染色纤维密度降低了20 - 25%。虽然在V/VI层中AChE阳性纤维和银染色纤维的损失显著相关，但线性回归分析表明，AChE阳性纤维的损失幅度大于根据正常纤维残余密度所预测的幅度。因此，数据表明向皮质注入192 IgG-皂草素不会导致非胆碱能传入神经的损失。向皮质内注入相对低浓度和小体积的192 IgG-皂草素似乎为研究特定皮质区域胆碱能输入的功能提供了一种有用的方法。
