Neuronal and Glial Distribution of Tau Protein in the Adult Rat and Monkey.
Neuronal and Glial Distribution of Tau Protein in the Adult Rat and Monkey.
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DOI：
10.3389/fnmol.2021.607303
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发表时间：
2021
影响因子：
4.8
通讯作者：
Grabinski T
中科院分区：
文献类型：
--
作者：
Kanaan NM;Grabinski T
Tau是一种微管相关蛋白，其生理功能仍然是一个积极研究的主题。此外，tau蛋白是几种疾病如阿尔茨海默病和几种额颞叶痴呆的发病机制中的核心参与者。在生理和疾病背景下理解tau的一个关键变量是其在成人CNS细胞内的正常定位。Tau通常被描述为轴突特异性（或富集）和神经元特异性蛋白，在神经胶质细胞中几乎没有表达，所有这些都是不真实的。了解正常的tau分布也会影响实验结果的解释和关于其在疾病中作用的假设。因此，我们开始帮助澄清正常定位的tau蛋白在成年中枢神经系统的中年大鼠和恒河猴使用海马作为一个代表性的大脑结构。通过定量夹心ELISA测定，大鼠海马中tau的生理浓度为6.6 μM，白色物质中为3.6 μM。我们使用具有不同区域表位的多种tau特异性抗体评估了tau的细胞定位，包括Tau 1，Tau 5，Tau 7，R1和两种新型灵长类特异性抗体NT 9和NT 15。在大鼠和猴中，tau蛋白定位于体树突和轴突隔室以及神经元核的子集内。半定量荧光强度测量显示，取决于所使用的特定试剂，体树突tau相对等于、高于或低于轴突tau，突出显示了tau与各种抗体的差异标记，尽管其分布在整个神经元中。Tau在成熟的少突胶质细胞中强烈表达，并且在少突胶质细胞前体细胞、星形胶质细胞或小胶质细胞中几乎不表达。总的来说，数据表明tau在生理条件下为0.3 - 7 μM，在轴突中没有特异性富集，并且通常在成年CNS的神经元和成熟少突胶质细胞中发现。tau分布的完整景观不是由所有抗体揭示的，这表明表位的可用性在特定神经元隔室中是不同的。这些发现为更好地理解正常tau分布和解释疾病条件下不同隔室或细胞类型中tau存在的数据奠定了基础。
Tau is a microtubule-associated protein for which the physiological functions remain a topic of vigorous investigation. Additionally, tau is a central player in the pathogenesis of several diseases such as Alzheimer’s disease and several frontotemporal dementias. A critical variable to understanding tau in physiological and disease contexts is its normal localization within cells of the adult CNS. Tau is often described as an axon-specific (or enriched) and neuron-specific protein with little to no expression in glial cells, all of which are untrue. Understanding normal tau distribution also impacts interpretation of experimental results and hypotheses regarding its role in disease. Thus, we set out to help clarify the normal localization of tau in the adult CNS of middle-aged rats and rhesus macaque using the hippocampus as a representative brain structure. The physiological concentration of tau in the rat hippocampus was 6.6 μM and in white matter was 3.6 μM as determined by quantitative sandwich ELISAs. We evaluated the cellular localization of tau using multiple tau-specific antibodies with epitopes to different regions, including Tau1, Tau5, Tau7, R1, and two novel primate-specific antibodies NT9 and NT15. In the rat and monkey, tau was localized within the somatodendritic and axonal compartments, as well as a subset of neuronal nuclei. Semi-quantitative fluorescence intensity measurements revealed that depending on the specific reagent used the somatodendritic tau is relatively equal to, higher than, or lower than axonal tau, highlighting differential labeling of tau with various antibodies despite its distribution throughout the neuron. Tau was strongly expressed in mature oligodendrocytes and displayed little to no expression in oligodendrocyte precursor cells, astrocytes or microglia. Collectively, the data indicate tau is ∼3 – 7 μM under physiological conditions, is not specifically enriched in axons, and is normally found in both neurons and mature oligodendrocytes in the adult CNS. The full landscape of tau distribution is not revealed by all antibodies suggesting availability of the epitopes is different within specific neuronal compartments. These findings set the stage for better understanding normal tau distributions and interpreting data regarding the presence of tau in different compartments or cell types within disease conditions.
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影响因子：
6.1
作者：
Combs B;Hamel C;Kanaan NM
通讯作者：
Kanaan NM
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
影响因子：
--
作者：
Combs B;Tiernan CT;Hamel C;Kanaan NM
通讯作者：
Kanaan NM
影响因子：
2.9
作者：
BUSCIGLIO, J;FERREIRA, A;CACERES, A
通讯作者：
CACERES, A
影响因子：
12.7
作者：
DICKSON, DW;KSIEZAKREDING, H;YEN, SH
通讯作者：
YEN, SH