Wiley R G, Berbos T G, Deckwerth T L, Johnson E M, Lappi D A
Laboratory of Experimental Neurology, DVAMC, Nashville, TN 37212-2637, USA.
J Neurol Sci. 1995 Feb;128(2):157-66. doi: 10.1016/0022-510x(94)00226-e.
Degeneration of cholinergic neurons in the basal forebrain (CBF) is a prominent neuropathological feature of Alzheimer's disease and is thought responsible for some cognitive deficits seen in patients. An animal model of pure CBF degeneration would be valuable for analysis of the function of these neurons and testing therapeutic strategies. CBF neurons express receptors for nerve growth factor. In order to selectively destroy these neurons, we developed an immunotoxin using monoclonal antibody (192 IgG) to rat NGF receptor (p75NGFr) armed with the ribosome inactivating protein, saporin. In vitro 192-saporin was highly toxic to neurons expressing p75NGFr. Intraventricular injections of 192-saporin destroyed the CBF and impaired passive avoidance learning. These results indicate that 192-saporin treated rats can be used to model a key feature of Alzheimer's disease and that anti-neuronal immunotoxins are a powerful approach to selective neural lesioning.
基底前脑（CBF）胆碱能神经元的退化是阿尔茨海默病的一个显著神经病理学特征，并且被认为是导致患者出现某些认知缺陷的原因。纯CBF退化的动物模型对于分析这些神经元的功能以及测试治疗策略将是有价值的。CBF神经元表达神经生长因子的受体。为了选择性地破坏这些神经元，我们利用针对大鼠神经生长因子受体（p75NGFr）的单克隆抗体（192 IgG）与核糖体失活蛋白皂草素构建了一种免疫毒素。在体外，192 - 皂草素对表达p75NGFr的神经元具有高度毒性。脑室内注射192 - 皂草素会破坏CBF并损害被动回避学习。这些结果表明，经192 - 皂草素处理的大鼠可用于模拟阿尔茨海默病的一个关键特征，并且抗神经元免疫毒素是一种用于选择性神经损伤的有效方法。
