少突胶质前体细胞中 MCT1 的缺失导致迟发性少突胶质细胞髓鞘形成障碍和轴突变性。
MCT1 Deletion in Oligodendrocyte Lineage Cells Causes Late-Onset Hypomyelination and Axonal Degeneration.
机构信息
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
出版信息
Cell Rep. 2021 Jan 12;34(2):108610. doi: 10.1016/j.celrep.2020.108610.
Oligodendrocytes (OLs) are important for myelination and shuttling energy metabolites lactate and pyruvate toward axons through their expression of monocarboxylate transporter 1 (MCT1). Recent studies suggest that loss of OL MCT1 causes axonal degeneration. However, it is unknown how widespread and chronic loss of MCT1 in OLs specifically affects neuronal energy homeostasis with aging. To answer this, MCT1 conditional null mice were generated that allow for OL-specific MCT1 ablation. We observe that MCT1 loss from OL lineage cells is dispensable for normal myelination and axonal energy homeostasis early in life. By contrast, loss of OL lineage MCT1 expression with aging leads to significant axonal degeneration with concomitant hypomyelination. These data support the hypothesis that MCT1 is important for neuronal energy homeostasis in the aging central nervous system (CNS). The reduction in OL MCT1 that occurs with aging may enhance the risk for axonal degeneration and atrophy in neurodegenerative diseases.
少突胶质细胞（OLs）对于髓鞘形成和通过其表达的单羧酸转运蛋白 1（MCT1）将能量代谢物乳酸盐和丙酮酸转运到轴突很重要。最近的研究表明，OLs 的 MCT1 缺失会导致轴突变性。然而，尚不清楚 OLs 中 MCT1 的广泛和慢性缺失如何特别影响衰老时神经元的能量稳态。为了回答这个问题，生成了允许 OL 特异性 MCT1 消融的 MCT1 条件性缺失小鼠。我们观察到，OL 谱系细胞中 MCT1 的缺失对于正常髓鞘形成和轴突能量稳态在生命早期是可有可无的。相比之下，随着年龄的增长，OL 谱系 MCT1 表达的缺失会导致明显的轴突变性，同时伴有髓鞘减少。这些数据支持 MCT1 对于衰老中枢神经系统（CNS）中神经元能量稳态很重要的假设。衰老时发生的 OL MCT1 减少可能会增加神经退行性疾病中轴突变性和萎缩的风险。
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