Background:Human tauopathy brain injections into the mouse brain induce the development of tau aggregates, which spread to functionally connected brain regions; however, the features of this neurotoxicity remain unclear. One reason may be short observational periods because previous studies mostlyused mutated-tau transgenic mice and needed to complete the study before these mice developed neurofibrillary tangles. Objective:To examine whether long-term incubation of Alzheimer’s disease (AD) brain in the mouse brain cause functional decline. Methods:We herein used Tg601 mice, which overexpress wild-type human tau, and non-transgenic littermates (NTg) and injected an insoluble fraction of the AD brain into the unilateral hippocampus. Results:After a long-term (17–19 months) post-injection, mice exhibited learning deficits detected by the Barnes maze test. Aggregated tau pathology in the bilateral hippocampus was more prominent in Tg601 mice than in NTg mice. No significant changes were observed in the number of Neu-N positive cells or astrocytes in the hippocampus, whereas that of Iba-I-positive microglia increased after the AD brain injection. Conclusion:These results potentially implicate tau propagation in functional decline and indicate that long-term changes in non-mutated tau mice may reflect human pathological conditions.

中文翻译：

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在小鼠脑中长期注射阿尔茨海默病脑提取物后伴随小胶质细胞增殖的学习缺陷

背景：人类 tau 病脑注射到小鼠大脑中会诱导 tau 聚集体的发展，这些聚集体扩散到功能连接的大脑区域；然而，这种神经毒性的特征仍不清楚。一个原因可能是观察期短，因为以前的研究主要使用突变的 tau 转基因小鼠，并且需要在这些小鼠出现神经原纤维缠结之前完成研究。目的：研究阿尔茨海默病（AD）脑在小鼠脑中长期潜伏是否会导致功能衰退。方法：我们在此使用 Tg601 小鼠，其过度表达野生型人类 tau 和非转基因同窝仔 (NTg)，并将 AD 脑的不溶性部分注射到单侧海马中。结果：经过长期（17-19 个月）注射后，小鼠表现出通过巴恩斯迷宫测试检测到的学习缺陷。与 NTg 小鼠相比，Tg601 小鼠双侧海马中聚集的 tau 病理学更为突出。海马中 Neu-N 阳性细胞或星形胶质细胞的数量没有观察到显着变化，而在 AD 脑注射后，Iba-I 阳性小胶质细胞的数量增加。结论：这些结果可能暗示 tau 增殖与功能衰退有关，并表明非突变 tau 小鼠的长期变化可能反映了人类病理状况。