Hyperphosphorylated tau in parahippocampal cortex impairs place learning in aged mice expressing wild-type human tau
Hyperphosphorylated tau in parahippocampal cortex impairs place learning in aged mice expressing wild-type human tau
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DOI：
10.1038/sj.emboj.7601917
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发表时间：
2007-12-12
期刊：
影响因子：
11.4
通讯作者：
Takashima, Akihiko
中科院分区：
文献类型：
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作者：
Kimura, Tetsuya;Yamashita, Shunji;Takashima, Akihiko
为了研究tau蛋白如何影响神经元缠结（NFT）形成过程中的神经功能，我们检查了表达野生型人tau蛋白的小鼠的行为，神经活动和神经病理学。在这里，我们证明老年（420个月大）小鼠表现出位置学习和记忆受损，尽管它们没有形成NFT或表现出神经元丢失。然而，可溶性过度磷酸化的tau蛋白和突触丢失被发现在相同的区域。锰增强MRI显示海马旁区的活动与Morris水迷宫评估的记忆下降密切相关。两者合计，过度磷酸化的tau蛋白的积累和突触丢失在老年小鼠中，导致海马旁区域（包括内嗅皮层）的神经活动抑制，可能是位置学习障碍的基础。因此，内嗅皮层中NFT形成之前发生的过度磷酸化tau的积累可能有助于阿尔茨海默病（AD）中所见的记忆问题。
To investigate how tau affects neuronal function during neurofibrillary tangle (NFT) formation, we examined the behavior, neural activity, and neuropathology of mice expressing wild-type human tau. Here, we demonstrate that aged (420 months old) mice display impaired place learning and memory, even though they do not form NFTs or display neuronal loss. However, soluble hyperphosphorylated tau and synapse loss were found in the same regions. Mn-enhanced MRI showed that the activity of the parahippocampal area is strongly correlated with the decline of memory as assessed by the Morris water maze. Taken together, the accumulation of hyperphosphorylated tau and synapse loss in aged mice, leading to inhibition of neural activity in parahippocampal areas, including the entorhinal cortex, may underlie place learning impairment. Thus, the accumulation of hyperphosphorylated tau that occurs before NFT formation in entorhinal cortex may contribute to the memory problems seen in Alzheimer's disease (AD).