Distribution of endogenous normal tau in the mouse brain.
Distribution of endogenous normal tau in the mouse brain.
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DOI：
10.1002/cne.24577
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发表时间：
2019-04-01
期刊：
影响因子：
--
通讯作者：
Miyasaka T
中科院分区：
文献类型：
--
作者：
Kubo A;Misonou H;Matsuyama M;Nomori A;Wada-Kakuda S;Takashima A;Kawata M;Murayama S;Ihara Y;Miyasaka T
Tau是一种微管相关蛋白（MAP），定位于轴突。在阿尔茨海默病（AD）中，tau蛋白的分布经历了显著的改变，导致体树突隔室中tau蛋白内含物的形成。虽然异常聚集的tau蛋白已在人类患者组织和AD动物模型中得到广泛研究，但由于正常未聚集的tau蛋白在体内的可检测性较差，因此尚未充分研究正常tau蛋白如何定位于轴突，这将是理解错误定位如何发生的基础。因此，我们开发了免疫组织化学技术，可以高灵敏度地检测正常小鼠和人脑组织中的tau蛋白。使用这些技术，我们证明了全球分布的tau蛋白在小鼠大脑中，并证实，正常的tau蛋白是专门本地化的轴突隔室在体内。有趣的是，tau抗体强烈标记无髓鞘轴突，如海马苔藓纤维，而白色物质通常表现出低水平的免疫反应性。此外，小鼠tau不仅在神经元中而且在少突胶质细胞中高度表达。使用刺激耗竭显微镜进行超分辨率成像，轴突tau呈现点状而非纤维状，表明tau稀疏地装饰微管。突触前和突触后标记物的共标记揭示了正常tau不局限于突触，而是稀疏地分布在轴突中。总之，本研究报告了研究tau在体内的定位和错误定位的新型抗体以及小鼠脑中正常tau定位的新发现。
Tau is a microtubule‐associated protein (MAP) that is localized to the axon. In Alzheimer's disease (AD), the distribution of tau undergoes a remarkable alteration, leading to the formation of tau inclusions in the somatodendritic compartment. While the abnormal aggregated tau has been extensively studied in human patient tissues and animal models of AD, how normal tau localizes to the axon, which would be the foundation to understand how the mis‐localization occurs, has not been well studied due to the poor detectability of normal unaggregated tau in vivo. Therefore, we developed immunohistochemical techniques that can detect normal mouse and human tau in brain tissues with high sensitivity. Using these techniques, we demonstrate the global distribution of tau in the mouse brain and confirmed that normal tau is exclusively localized to the axonal compartment in vivo. Interestingly, tau antibodies strongly labeled nonmyelinated axons such as hippocampal mossy fibers, while white matters generally exhibited low levels of immunoreactivity. Furthermore, mouse tau is highly expressed not only in neurons but also in oligodendrocytes. With super resolution imaging using the stimulated‐depletion microscopy, axonal tau appeared punctate rather than fibrous, indicating that tau decorates microtubules sparsely. Co‐labeling with presynaptic and postsynaptic markers revealed that normal tau is not localized to synapses but sparsely distributes in the axon. Taken together, this study reports novel antibodies to investigate the localization and mis‐localization of tau in vivo and novel findings of normal tau localization in the mouse brain.
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DOI：
10.1083/jcb.101.4.1371
发表时间：
1985-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Binder LI;Frankfurter A;Rebhun LI
通讯作者：
Rebhun LI
DOI：
10.1523/jneurosci.4101-08.2008
发表时间：
2008-11-26
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Planel E;Krishnamurthy P;Miyasaka T;Liu L;Herman M;Kumar A;Bretteville A;Figueroa HY;Yu WH;Whittington RA;Davies P;Takashima A;Nixon RA;Duff KE
通讯作者：
Duff KE
影响因子：
16.2
作者：
Hoover, Brian R.;Reed, Miranda N.;Su, Jianjun;Penrod, Rachel D.;Kotilinek, Linda A.;Grant, Marianne K.;Pitstick, Rose;Carlson, George A.;Lanier, Lorene M.;Yuan, Li-Lian;Ashe, Karen H.;Liao, Dezhi
通讯作者：
Liao, Dezhi
影响因子：
6.1
作者：
Miyasaka, T;Ding, Z;Ihara, Y
通讯作者：
Ihara, Y
影响因子：
4.8
作者：
Deshpande, Atul;Win, Khin May;Busciglio, Jorge
通讯作者：
Busciglio, Jorge