Mandel R J, Gage F H, Clevenger D G, Spratt S K, Snyder R O, Leff S E
Department of Preclinical Biology, Cell Genesys Incorporated, 342 Lakeside Drive, Foster City, California, 94404, USA.
Exp Neurol. 1999 Jan;155(1):59-64. doi: 10.1006/exnr.1998.6961.
Nerve growth factor (NGF) has been shown to support the survival of axotomized medial septal cholinergic neurons after aspirative lesions of the fimbria-fornix (FF). This survival effect has been achieved utilizing intraventricular and intraparenchymal delivery of the NGF protein. While the use of NGF for the treatment of the cholinergic deficits present in Alzheimer's disease shows promise based on its efficacy in animal models, concerns about side-effects of intraventricular NGF delivery in humans have been raised. In the present study, NGF was delivered directly to the medial septum via a recombinant adeno-associated viral vector (rAAV) encoding the cDNA for human NGF prior to a FF lesion in rats. This rAAV-mediated NGF delivery was shown to significantly attenuate the medial septal cholinergic cell loss observed in animals receiving an equivalent injection of a control rAAV vector.
神经生长因子（NGF）已被证明可支持穹窿海马伞（FF）抽吸损伤后被切断轴突的内侧隔胆碱能神经元的存活。通过脑室内和脑实质内递送NGF蛋白已实现这种存活效应。虽然基于NGF在动物模型中的功效，其用于治疗阿尔茨海默病中存在的胆碱能缺陷显示出前景，但人们对人脑中脑室内递送NGF的副作用表示担忧。在本研究中，在大鼠FF损伤之前，通过编码人NGF cDNA的重组腺相关病毒载体（rAAV）将NGF直接递送至内侧隔。结果显示，这种rAAV介导的NGF递送可显著减轻在接受等量对照rAAV载体注射的动物中观察到的内侧隔胆碱能细胞损失。
