Intranasal administration of nerve growth factor (NGF) rescues recognition memory deficits in AD11 anti-NGF transgenic mice
Intranasal administration of nerve growth factor (NGF) rescues recognition memory deficits in AD11 anti-NGF transgenic mice
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DOI：
10.1073/pnas.0500195102
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发表时间：
2005-03-08
影响因子：
11.1
通讯作者：
Cattaneo, A
中科院分区：
文献类型：
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作者：
De Rosa, R;Garcia, AA;Cattaneo, A
将神经生长因子（NGF）输送到患者大脑似乎是治疗阿尔茨海默病（AD）等神经退行性疾病的一种新兴的潜在治疗方法。鼻内给药途径可以提供脑室内输注和基因治疗的替代方案。我们之前表明，鼻内给予 NGF 可改善 AD11 小鼠的胆碱能缺陷，并减少磷酸化阳性神经元的数量和 β-淀粉样蛋白的积累，这些小鼠表达中和 NGF 作用的转基因抗体，并表现出进行性阿尔茨海默样神经变性。在这项研究中，我们报告称，AD11 小鼠的阿尔茨海默样神经变性与从 4 个月大开始的视觉识别记忆和空间记忆的进行性行为缺陷有关。为了确定在出现第一次记忆缺陷后开始鼻内给予 NGF 是否可以恢复 AD11 小鼠的认知缺陷，我们评估了 NGF 治疗或对照 AD11 小鼠在物体识别测试以及位置和背景记忆测试中的表现。未经治疗的 AD11 小鼠表现出的缺陷可以通过鼻内施用 NGF 来弥补。因此，从治疗角度来看，这种给药途径提供了一种将 NGF 递送至大脑的有前途的方法。
Nerve growth factor (NGF) delivery to the brain of patients appears to be an emerging potential therapeutic approach to neurodegenerative disease, such as Alzheimer's disease (AD). The intranasal route of administration could provide an alternative to intracerebroventricular infusion and gene therapy. We previously showed that intranasal administration of NGF determined an amelioration of cholinergic deficit and a decrease in the number of phosphotaupositive neurons and of beta-amyloid accumulation in AD11 mice, which express transgenic antibodies neutralizing NGF action and exhibit a progressive Alzheimer-like neurodegeneration. In this study, we report that the Alzheimer-like neurodegeneration in AD11 mice is linked to progressive behavioral deficits in visual recognition memory and spatial memory starting from 4 months of age. To establish whether intranasal administration of NGF, started after the appearance of the first memory deficits, could revert the cognitive deficits in AD11 mice, we assessed the performance of NGF-treated or control AD11 mice in the object recognition test and in a test of memory for place and context. Deficits exhibited by untreated AD11 mice could be rescued by the intranasal administration of NGF. Thus, this route of administration provides a promising way to deliver NGF to the brain in a therapeutic perspective.