Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity.
Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity.
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DOI：
10.1038/nature11007
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发表时间：
2012-04-29
期刊：
影响因子：
64.8
通讯作者：
Nave, Klaus-Armin
中科院分区：
文献类型：
--
作者：
Fuenfschilling, Ursula;Supplie, Lotti M.;Mahad, Don;Boretius, Susann;Saab, Aiman S.;Edgar, Julia;Brinkmann, Bastian G.;Kassmann, Celia M.;Tzvetanova, Iva D.;Moebius, Wiebke;Diaz, Francisca;Meijer, Dies;Suter, Ueli;Hamprecht, Bernd;Sereda, Michael W.;Moraes, Carlos T.;Frahm, Jens;Goebbels, Sandra;Nave, Klaus-Armin
少突胶质细胞是中枢神经系统的髓鞘形成胶质细胞，维持长期的轴突完整性。然而，根本的支持机制还不清楚。在这里，我们通过产生条件性Cox 10（血红素IX法尼基转移酶）突变小鼠，其中少突胶质细胞和许旺细胞不能组装稳定的线粒体细胞色素c氧化酶（考克斯，也称为线粒体复合物IV），确定轴突-神经胶质细胞相互作用的代谢成分。在周围神经系统中，Cox 10条件突变体表现出严重的神经病变，伴有髓鞘形成障碍、异常Remak束、肌肉萎缩和瘫痪。值得注意的是，干扰线粒体呼吸并不导致神经胶质细胞死亡。在成人中枢神经系统，我们没有发现脱髓鞘，轴突变性或继发性炎症的迹象。与对考克斯抑制剂敏感的培养的少突胶质细胞不同，髓鞘形成后的少突胶质细胞在没有考克斯活性的情况下存活良好。更重要的是，通过体内磁共振光谱，与对照组相比，脑乳酸浓度增加，但仅在暴露于挥发性麻醉剂的小鼠中检测到。这表明少突胶质细胞的有氧糖酵解产物在白色物质束内快速代谢。由于髓鞘轴突在能量缺乏时可以利用乳酸，我们的研究结果提示了一个轴突-神经胶质代谢偶联发挥生理功能的模型。
Oligodendrocytes, the myelin-forming glial cells of the central nervous system, maintain long-term axonal integrity. However, the underlying support mechanisms are not understood. Here we identify ametabolic component of axon–glia interactions by generating conditional Cox10 (protoheme IX farnesyltransferase) mutant mice, in which oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX, also known as mitochondrial complex IV). In the peripheral nervous system, Cox10 conditional mutants exhibit severe neuropathy with dysmyelination, abnormal Remak bundles, muscle atrophy and paralysis. Notably, perturbing mitochondrial respiration did not cause glial cell death. In the adult central nervous system, we found no signs of demyelination, axonal degeneration or secondary inflammation. Unlike cultured oligodendrocytes, which are sensitive to COX inhibitors, post-myelination oligodendrocytes survive well in the absence of COX activity. More importantly, by in vivo magnetic resonance spectroscopy, brain lactate concentrations inmutants were increased compared with controls, but were detectable only in mice exposed to volatile anaesthetics. This indicates that aerobic glycolysis products derived from oligodendrocytes are rapidly metabolized within white matter tracts. Becausemyelinated axons can use lactate when energy-deprived, our findings suggest a model in which axon– glia metabolic coupling serves a physiological function.
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影响因子：
5.3
作者：
Diaz, Francisca;Fukui, Hirokazu;Moraes, Carlos T.
通讯作者：
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影响因子：
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作者：
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