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轴突黏附分子在中枢神经系统髓鞘形成中的关键作用

[Pivotal role of axonal adhesion molecules in central nervous system myelination].

作者信息

Lubetzki C, Charles P, Stankoff B, Hernandez P, Zalc B

机构信息

INSERM U-495, Hôpital de la Salpêriére, Paris.

出版信息

Neurol Neurochir Pol. 2000;34(3 Suppl):41-4.

PMID:10983299
Abstract

Close relationship between neurons and oligodendrocytes seems to be of the greatest importance during oligodendrocyte maturation and myelin formation within central nervous system. Two major factors are likely to play the decisive role in CNS myelination--adhesion molecules and electrical activity. It has been shown, both in vitro and in vivo, that blocking or stimulating electrical activity may inhibit or induce myelination respectively. The fact that even in culture oligodendrocytes myelinate solely axons and not other cellular processes present within CNS as well as the finding that normal myelin sheath compaction is encountered only around axons suggest that close interaction between oligodendrocytes and neurons is required for normal myelin formation. Adhesion molecules are most likely involved in this interaction by not only bringing the axon and the glial cell close to each other but also by transducing signals to initiate myelination. The neural cell adhesion molecule (NCAM) is a candidate molecule that could regulate axon/glial cell interaction. It is abundantly present in all growing fiber tracts of the developing CNS. Since its polysialylated from (PSA-NCAM) has been shown to disappear from axonal surface as myelination progresses and that its removal increases 4 to 5 fold myelination, it is thought to be a negative factor for myelin formation. These observations may have important implications in therapeutic strategies in demyelinating disorders like multiple sclerosis.

摘要

在中枢神经系统中,少突胶质细胞成熟和髓鞘形成过程中,神经元与少突胶质细胞之间的密切关系似乎至关重要。两个主要因素可能在中枢神经系统髓鞘形成中起决定性作用——黏附分子和电活动。体外和体内研究均表明,阻断或刺激电活动可能分别抑制或诱导髓鞘形成。即使在培养环境中,少突胶质细胞也仅使轴突髓鞘化,而不会使中枢神经系统中存在的其他细胞突起髓鞘化,以及正常髓鞘紧密层仅出现在轴突周围这一发现表明,少突胶质细胞与神经元之间的密切相互作用是正常髓鞘形成所必需的。黏附分子很可能通过不仅使轴突和神经胶质细胞彼此靠近,还通过转导信号来启动髓鞘形成而参与这种相互作用。神经细胞黏附分子(NCAM)是一种可能调节轴突/神经胶质细胞相互作用的候选分子。它大量存在于发育中的中枢神经系统所有生长的纤维束中。由于其多唾液酸化形式(PSA-NCAM)已被证明随着髓鞘形成的进展从轴突表面消失,并且其去除会使髓鞘形成增加4至5倍,因此它被认为是髓鞘形成的负性因素。这些观察结果可能对脱髓鞘疾病如多发性硬化症的治疗策略具有重要意义。

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