Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, Hong Kong.
Glia. 2020 Jan;68(1):161-177. doi: 10.1002/glia.23710. Epub 2019 Aug 27.
Schwann cell (SC)-specific monocarboxylate transporter 1 (MCT1) knockout mice were generated by mating MCT1 mice with myelin protein zero (P0)-Cre mice. P0-Cre , MCT1 mice have no detectable early developmental defects, but develop hypomyelination and reduced conduction velocity in sensory, but not motor, peripheral nerves during maturation and aging. Furthermore, reduced mechanical sensitivity is evident in aged P0-Cre , MCT1 mice. MCT1 deletion in SCs impairs both their glycolytic and mitochondrial functions, leading to altered lipid metabolism of triacylglycerides, diacylglycerides, and sphingomyelin, decreased expression of myelin-associated glycoprotein, and increased expression of c-Jun and p75-neurotrophin receptor, suggesting a regression of SCs to a less mature developmental state. Taken together, our results define the contribution of SC MCT1 to both SC metabolism and peripheral nerve maturation and aging.
施万细胞（SC）特异性单羧酸转运蛋白 1（MCT1）敲除小鼠通过交配 MCT1 小鼠与髓鞘蛋白零（P0）-Cre 小鼠产生。P0-Cre，MCT1 小鼠在早期发育过程中没有可检测到的缺陷，但在成熟和衰老过程中，感觉神经而非运动神经的髓鞘形成减少，传导速度降低。此外，在老年 P0-Cre，MCT1 小鼠中明显存在机械敏感性降低。SC 中的 MCT1 缺失会损害其糖酵解和线粒体功能，导致三酰甘油、二酰甘油和神经鞘磷脂的脂质代谢改变，髓鞘相关糖蛋白表达降低，c-Jun 和 p75 神经营养素受体表达增加，提示 SC 向更不成熟的发育状态回归。总之，我们的研究结果定义了 SC MCT1 对 SC 代谢和周围神经成熟和衰老的贡献。
