Identification of Tau protein as a novel marker for maturation and pathological changes of oligodendrocytes
Identification of Tau protein as a novel marker for maturation and pathological changes of oligodendrocytes
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DOI：
10.1002/glia.24322
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发表时间：
2022-12-24
期刊：
影响因子：
6.2
通讯作者：
Misonou，Hiroaki
中科院分区：
文献类型：
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作者：
Torii，Tomohiro;Miyamoto，Yuki;Misonou，Hiroaki
微管相关蛋白 Tau 主要在神经元轴突中表达，但也在成年啮齿动物和猴脑中的 Olig2 阳性少突胶质细胞中表达。在这项研究中，我们试图确定 Tau 在什么细胞阶段在少突胶质细胞谱系中表达。我们使用众所周知的少突胶质细胞谱系标记物对成年小鼠脑切片进行免疫染色，发现 Tau 在成熟的少突胶质细胞中表达，但在少突胶质细胞祖细胞和未成熟的前少突胶质细胞中不表达。我们还研究了发育中的小鼠大脑中 Tau 蛋白的表达。令人惊讶的是，Tau 表达发生在髓鞘形成高峰之后，甚至超过了 GSTπ 表达，GSTπ 表达被认为是髓鞘化少突胶质细胞的标志。这些结果表明 Tau 是少突胶质细胞成熟的新标志物。然后我们研究了 Tau 对少突胶质细胞发育和/或髓鞘形成是否重要以及 Tau 在脱髓鞘过程中如何变化。首先，我们发现 Tau 敲除小鼠的髓鞘形成和少突胶质细胞标记物没有变化，这表明 Tau 是可有可无的。接下来，我们分析了 Pelizaeus-Merzbacher 病（一种罕见的脑白质营养不良）的蛋白脂质蛋白 1 转基因模型。与野生型小鼠相比，半合子转基因小鼠中 Tau 阳性细胞的数量显着增加。这些细胞对 Olig2、CC1 和 GSTπ 也呈阳性，但对 PDGFRα 和 GPR17 不呈阳性。与此形成鲜明对比的是，在铜宗诱导的多发性硬化症模型中，Tau 以及 GSTπ 的表达水平显着降低。综上所述，我们建议 Tau 作为少突胶质细胞谱系的新标记物并用于研究脱髓鞘病变。
Microtubule‐associated protein Tau is primarily expressed in axons of neurons, but also in Olig2‐positive oligodendrocytes in adult rodent and monkey brains. In this study, we sought to determine at what cell stage Tau becomes expressed in the oligodendrocyte lineage. We performed immunostaining of adult mouse brain sections using well‐known markers of oligodendrocyte lineage and found that Tau is expressed in mature oligodendrocytes, but not in oligodendrocyte progenitors and immature pre‐oligodendrocytes. We also investigated Tau expression in developing mouse brain. Surprisingly, Tau expression occurred after the peak of myelination and even exceeded GSTπ expression, which has been considered as a marker of myelinating oligodendrocytes. These results suggest Tau as a novel marker of oligodendrocyte maturation. We then investigated whether Tau is important for oligodendrocyte development and/or myelination and how Tau changes in demyelination. First, we found no changes in myelination and oligodendrocyte markers in Tau knockout mice, suggesting that Tau is dispensable. Next, we analyzed the proteolipid protein 1 transgenic model of Pelizaeus‐Merzbacher disease, which is a rare leukodystrophy. In hemizygous transgenic mice, the number of Tau‐positive cells were significantly increased as compared with wild type mice. These cells were also positive for Olig2, CC1, and GSTπ, but not PDGFRα and GPR17. In stark contrast, the expression level of Tau, as well as GSTπ, was dramatically decreased in the cuprizone‐induced model of multiple sclerosis. Taken together, we propose Tau as a new marker of oligodendrocyte lineage and for investigating demyelination lesions.