Nakahara Jin, Takemura Masaaki, Gomi Hiroshi, Tsunematsu Ken-Ichiro, Itohara Shigeyoshi, Asou Hiroaki, Ogawa Masaharu, Aiso Sadakazu, Tan-Takeuchi Kyoko
Department of Anatomy, Keio University School of Medicine, Shinanomachi, Shinjuku, Tokyo, Japan.
J Neurosci Res. 2003 May 1;72(3):279-89. doi: 10.1002/jnr.10593.
Recent in vitro study showed that astrocytes induce oligodendrocyte processes to adhere to axons. However, the role of astrocytes in myelination in vivo remains unknown. We have, therefore, conducted a study to clarify the possible involvement of astrocytes during the initial myelination process. In newborn mice, the expression of glial fibrillary acidic protein (GFAP), a marker for astrocytes, was restricted to a few fibrous architectures in the subventricular zone (SVZ), but we did not observe any GFAP-positive astrocytes. Prior to the onset of myelination, GFAP became transiently expressed in the cells with radial fibers elongating from the SVZ to the pia of cerebral cortex, and myelin-associated glycoprotein (MAG)-positive premyelinating oligodendrocytes appeared as neighbors to them, with the processes attaching to radial fibers, but not to axons. These GFAP-positive "radial" cells lost their fibrous architecture and became typical GFAP-positive astrocytes at about 10 days postnatally, when myelination set in, indicating that the disappearance of radial fibers coordinates with the initiation of myelination. From these results, we propose that premyelinating oligodendrocytes are in contact with radial fibers rather than axons and that the cytoarchitectural transformation of radial fibers into astrocytes is involved substantially in controlling the onset of initial myelination. Our proposal was further confirmed by GFAP-deficient mice, in which the disappearance of these radial fibers and the initiation of myelination were delayed in parallel. Our findings together suggest that myelination in vivo is in concert with astrocytic differentiation, involving radial fibers therein, rather than being a mere axon-oligodendrocyte interaction.
最近的体外研究表明，星形胶质细胞可诱导少突胶质细胞突起黏附于轴突。然而，星形胶质细胞在体内髓鞘形成过程中的作用仍不清楚。因此，我们开展了一项研究，以阐明星形胶质细胞在初始髓鞘形成过程中可能发挥的作用。在新生小鼠中，星形胶质细胞标志物胶质纤维酸性蛋白（GFAP）的表达局限于脑室下区（SVZ）的一些纤维结构中，但我们未观察到任何GFAP阳性的星形胶质细胞。在髓鞘形成开始之前，GFAP在从SVZ向大脑皮质软膜延伸的放射状纤维细胞中短暂表达，并且髓鞘相关糖蛋白（MAG）阳性的前髓鞘形成少突胶质细胞出现在它们附近，其突起附着于放射状纤维而非轴突。这些GFAP阳性的“放射状”细胞在出生后约10天，即髓鞘形成开始时，失去其纤维结构并变成典型的GFAP阳性星形胶质细胞，这表明放射状纤维的消失与髓鞘形成的开始相协调。根据这些结果，我们提出前髓鞘形成少突胶质细胞与放射状纤维而非轴突接触，并且放射状纤维向星形胶质细胞的细胞结构转变在很大程度上参与控制初始髓鞘形成的开始。GFAP缺陷小鼠进一步证实了我们的推测，在这些小鼠中，这些放射状纤维的消失和髓鞘形成的开始同时延迟。我们的研究结果共同表明，体内髓鞘形成与星形胶质细胞分化协同进行，其中涉及放射状纤维，而不仅仅是轴突 - 少突胶质细胞的相互作用。
