Department of Anatomy and Neuroscience, Nara Medical University, Faculty of Medicine, 840 Shijo-cho, Kashihara City, Nara, 634-8521, Japan.
Neurochem Res. 2022 Sep;47(9):2826-2838. doi: 10.1007/s11064-022-03676-z. Epub 2022 Jul 20.
Cells in the white matter of the adult brain have a characteristic distribution pattern in which several cells are contiguously connected to each other, making a linear array (LA) resembling pearls-on-a-string parallel to the axon axis. We have been interested in how this pattern of cell distribution changes during aging and remyelination after demyelination. In the present study, with a multiplex staining method, semi-quantitative analysis of the localization of oligodendrocyte lineage cells (oligodendrocyte progenitors, premyelinating oligodendrocytes, and mature oligodendrocytes), astrocytes, and microglia in 8-week-old (young adult) and 32-week-old (aged) corpus callosum showed that young adult cells still include immature oligodendrocytes and that LAs contain a higher proportion of microglia than isolated cells. In aged mice, premyelinating oligodendrocytes were decreased, but microglia continued to be present in the LAs. These results suggest that the presence of microglia is important for the characteristic cell localization pattern of LAs. In a cuprizone-induced demyelination model, we observed re-formation of LAs after completion of cuprizone treatment, concurrent with remyelination. These re-formed LAs again contained more microglia than the isolated cells. This finding supports the hypothesis that microglia contribute to the formation and maintenance of LAs. In addition, regardless of the distribution of cells (LAs or isolated cells), astrocytes were found to be more abundant than in the normal corpus callosum at 24 weeks after cuprizone treatment when remyelination is completed. This suggests that astrocytes are involved in maintaining the functions of remyelinated white matter.
大脑白质中的细胞具有特征性的分布模式，其中几个细胞连续地彼此连接，形成类似于珠串的线性排列（LA），与轴突轴平行。我们一直对这种细胞分布模式在衰老和脱髓鞘后再髓鞘化过程中的变化感兴趣。在本研究中，我们采用多重染色方法，对半定量分析 8 周龄（年轻成年）和 32 周龄（老年）胼胝体中少突胶质细胞谱系细胞（少突胶质前体细胞、前髓鞘化少突胶质细胞和成熟少突胶质细胞）、星形胶质细胞和小胶质细胞的定位，结果显示年轻成年细胞中仍包含未成熟的少突胶质细胞，且 LA 中包含更高比例的小胶质细胞，高于分离的细胞。在老年小鼠中，前髓鞘化少突胶质细胞减少，但小胶质细胞仍存在于 LA 中。这些结果表明小胶质细胞的存在对于 LA 的特征性细胞定位模式很重要。在铜诱导脱髓鞘模型中，我们观察到在完成铜处理后，LA 重新形成，伴随着再髓鞘化。这些重新形成的 LA 再次包含比分离的细胞更多的小胶质细胞。这一发现支持了小胶质细胞有助于 LA 的形成和维持的假说。此外，无论细胞分布（LA 或分离的细胞）如何，在完成铜处理后 24 周即再髓鞘化完成时，星形胶质细胞的数量比正常胼胝体中更丰富。这表明星形胶质细胞参与维持再髓鞘化白质的功能。
