首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >Maturation of oligodendrocytes is more sensitive to TNF alpha than is survival of precursors and immature oligodendrocytes.
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Maturation of oligodendrocytes is more sensitive to TNF alpha than is survival of precursors and immature oligodendrocytes.

机译:与前体和未成熟少突胶质细胞的存活相比,少突胶质细胞的成熟对TNFα更敏感。

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摘要

TNF alpha is a cytokine recently found at high levels in multiple sclerosis plaques. The present study addressed the questions whether TNF alpha might affect oligodendrocytes at various stages of maturation and whether the effects of transient incubation with TNF alpha would last during subsequent differentiation. Primary glial-cell cultures were treated with 1000 U/ml of TNF alpha for 48 h, beginning on days 1, 2, 6, 8 and 10 days in vitro, and allowed to grow for up to 3 weeks (total) in vitro. A significant deficit of O4+/MBP+ cells in the TNF alpha-treated cultures became obvious during the second week. Moreover, the morphology of the O4-positive cells became more complex with time in the control cultures, whereas fewer cells in TNF alpha-treated cultures developed into cells with sheets of membrane or > four processes. In TNF alpha-treated cultures, the numbers of O4-positive cells increased by about four-fold during weeks 2 and 3, but the numbers of MBP-positive cells did not and were significantly lower than the numbers of MBP-positive cells in control cultures. The effects of TNF alpha were apparent 1 to 14 days after treatment, suggesting long-term influences, and could be initiated at diverse stages of maturation. Future testing of hypothetical mechanisms by which TNF alpha may inhibit oligodendrocyte differentiation should impact on our understanding of the apparent limitations on remyelination in the mature CNS.
机译:TNFα是最近在多发性硬化斑块中高水平发现的一种细胞因子。本研究解决了以下问题:TNFα是否可能在成熟的各个阶段影响少突胶质细胞,以及在随后的分化过程中与TNFα短暂孵育的影响是否会持续。从体外第1、2、6、8和10天开始,用1000 U / ml TNFα处理原代神经胶质细胞培养物48小时,并使其在体外最多生长3周(总计)。在第二周内,TNFα处理的培养物中O4 + / MBP +细胞明显不足。此外,在对照培养物中,O4阳性细胞的形态随着时间的推移变得更加复杂,而在TNFα处理的培养物中,较少的细胞发育成具有膜片或> 4个过程的细胞。在TNFα处理的培养物中,O4阳性细胞的数量在第2周和第3周增加了约四倍,但MBP阳性细胞的数量没有增加,并且显着低于对照组中的MBP阳性细胞的数量。文化。治疗后1至14天,TNFα的作用很明显,表明具有长期影响,并可在成熟的各个阶段开始。 TNFα可能抑制少突胶质细胞分化的假想机制的未来测试应影响我们对成熟CNS中髓鞘再生的明显限制的理解。

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