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Oligodendroglia metabolically support axons and contribute to neurodegeneration

机译:少突棘代谢支持轴突并促进神经变性

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摘要

Oligodendroglia support axon survival and function through mechanisms independent of myelination, and their dysfunction leads to axon degeneration in several diseases. The cause of this degeneration has not been determined, but lack of energy metabolites such as glucose or lactate has been proposed. Lactate is transported exclusively by monocarboxylate transporters, and changes to these transporters alter lactate production and use. Here we show that the most abundant lactate transporter in the central nervous system, monocarboxylate transporter 1 (MCT1, also known as SLC16A1), is highly enriched within oligodendroglia and that disruption of this transporter produces axon damage and neuron loss in animal and cell culture models. In addition, this same transporter is reduced in patients with, and in mouse models of, amyotrophic lateral sclerosis, suggesting a role for oligodendroglial MCT1 in pathogenesis. The role of oligodendroglia in axon function and neuron survival has been elusive; this study defines a new fundamental mechanism by which oligodendroglia support neurons and axons.
机译:少突棘通过独立于髓鞘形成的机制来支持轴突的存活和功能,并且它们的功能障碍导致某些疾病中的轴突变性。该变性的原因尚未确定,但已提出缺乏能量代谢物,例如葡萄糖或乳酸。乳酸仅通过单羧酸盐转运蛋白转运,这些转运蛋白的变化改变了乳酸的生产和使用。在这里,我们显示中枢神经系统中最丰富的乳酸转运蛋白,单羧酸盐转运蛋白1(MCT1,也称为SLC16A1),在少突胶质细胞中高度富集,这种转运蛋白的破坏在动物和细胞培养模型中产生轴突损伤和神经元丢失。 。此外,患有肌萎缩性侧索硬化的患者和小鼠模型中的这种转运蛋白减少,表明少突胶质MCT1在发病机理中的作用。少突神经胶质在轴突功能和神经元存活中的作用尚不清楚。这项研究定义了少突胶质细胞支持神经元和轴突的新的基本机制。

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  • 来源
    《Nature》 |2012年第7408期|p.443-448|共6页
  • 作者单位

    Department of Neurology, The Johns Hopkins University, 855 North Wolfe Street, Rangos 248, Baltimore, Maryland 21205, USA;

    Department of Neurology, The Johns Hopkins University, 855 North Wolfe Street, Rangos 248, Baltimore, Maryland 21205, USA;

    Department of Neurology, The Johns Hopkins University, 855 North Wolfe Street, Rangos 248, Baltimore, Maryland 21205, USA;

    School of Life Sciences, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne (EPFL), Station 19, CH-1015 Lausanne, Switzerland;

    Department of Neurology, The Johns Hopkins University, 855 North Wolfe Street, Rangos 248, Baltimore, Maryland 21205, USA;

    Department of Neurology, The Johns Hopkins University, 855 North Wolfe Street, Rangos 248, Baltimore, Maryland 21205, USA;

    Department of Neurology, The Johns Hopkins University, 855 North Wolfe Street, Rangos 248, Baltimore, Maryland 21205, USA;

    Department of Neurology, The Johns Hopkins University, 855 North Wolfe Street, Rangos 248, Baltimore, Maryland 21205, USA;

    Department of Neurology, The Johns Hopkins University, 855 North Wolfe Street, Rangos 248, Baltimore, Maryland 21205, USA;

    Department of Neurology, The Johns Hopkins University, 855 North Wolfe Street, Rangos 248, Baltimore, Maryland 21205, USA;

    Department of Physiology, University of Lausanne, 7 Rue du Bugnon, CH-1005 Lausanne, Switzerland;

    School of Life Sciences, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne (EPFL), Station 19, CH-1015 Lausanne, Switzerland;

    Department of Neurology, The Johns Hopkins University, 855 North Wolfe Street, Rangos 248, Baltimore, Maryland 21205, USA,Department of Neuroscience, The Johns Hopkins University, 855 North Wolfe Street, Rangos 270, Baltimore, Maryland 21205, USA,The Brain Science Institute, The Johns Hopkins University, 855 North Wolfe Street,Rangos 270, Baltimore, Maryland 21205, USA;

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