Haroutunian V, Zhou Y, Elder G, Li C, Lazzarini R A
Psychiatry Service, Bronx VA Medical Center, NY 10468, USA.
Brain Res Mol Brain Res. 1996 Nov;42(1):62-70. doi: 10.1016/s0169-328x(96)00114-3.
Previous studies have revealed that the transgenic mouse line expressing the human neurofilament-mid-sized (NF-M) gene evidences age-dependent and cell-specific pathological neurofibrillary accumulation in the central nerve system. In the current study, we investigated the learning and memory processes of NF-M transgenic mice at 3 and 8 months of age in a modified Morris water maze using a series of tasks including those primarily related to reference memory (i.e., spatial learning, reversal learning and probe trials) and to working memory (i.e., matching to sample tasks with or without delays). At 3 months of age, NF-M transgenic mice were indistinguishable from age- and litter-matched non-transgenic wild-type controls on any of the tests of reference and working memory. At 8 months of age, however, the NF-M transgenic mice exhibited significantly poorer performance than the age- and litter-matched wild-type control mice on both reference and working memory tasks. Immunohistological study of the brains of the 8-month-old NF-M transgenic mice revealed spherical and tangle-like neurofilamentous accumulation in their cerebral cortices. These results suggest that NF-M transgenic mice express both age-related histopathological changes and age-dependent learning and memory deficits. Whether NF-M transgenic mice exhibit even more severe behavioral impairments when they become aged is currently under study.
先前的研究表明，表达人类中分子量神经丝蛋白（NF-M）基因的转基因小鼠品系在中枢神经系统中表现出年龄依赖性和细胞特异性的病理性神经原纤维堆积。在本研究中，我们使用一系列任务，包括主要与参考记忆（即空间学习、逆向学习和探索试验）以及工作记忆（即有或无延迟的样本匹配任务）相关的任务，在改良的莫里斯水迷宫中研究了3个月和8个月大的NF-M转基因小鼠的学习和记忆过程。在3个月大时，NF-M转基因小鼠在参考记忆和工作记忆的任何测试中与年龄和同窝匹配的非转基因野生型对照没有区别。然而，在8个月大时，NF-M转基因小鼠在参考记忆和工作记忆任务上的表现明显比年龄和同窝匹配的野生型对照小鼠差。对8个月大的NF-M转基因小鼠大脑的免疫组织学研究显示，它们的大脑皮质中有球形和缠结状的神经丝堆积。这些结果表明，NF-M转基因小鼠表现出与年龄相关的组织病理学变化以及年龄依赖性的学习和记忆缺陷。NF-M转基因小鼠在衰老时是否会表现出更严重的行为障碍目前正在研究中。
