Monocarboxylate transporter 1 in Schwann cells contributes to maintenance of sensory nerve myelination during aging
Monocarboxylate transporter 1 in Schwann cells contributes to maintenance of sensory nerve myelination during aging
复制标题
DOI：
10.1002/glia.23710
复制
发表时间：
2019-08-27
期刊：
影响因子：
6.2
通讯作者：
Morrison, Brett M.
中科院分区：
文献类型：
--
作者：
Jha, Mithilesh Kumar;Lee, Youngjin;Morrison, Brett M.
通过将MCT 1（f/f）小鼠与髓磷脂蛋白零（P0）-Cre小鼠交配，产生雪旺细胞（SC）特异性单羧酸转运蛋白1（MCT 1）敲除小鼠。P0-Cre（+/-）、MCT 1（f/f）小鼠没有可检测到的早期发育缺陷，但在成熟和衰老过程中，感觉神经（而非运动神经）的髓鞘形成不足和传导速度降低。此外，老年P0-Cre（+/-）、MCT 1（f/f）小鼠的机械敏感性明显降低。SC中的MCT 1缺失损害了它们的糖酵解和线粒体功能，导致三酰甘油酯、二酰甘油酯和鞘磷脂的脂质代谢改变，髓鞘相关糖蛋白的表达降低，以及c-Jun和p75-神经营养因子受体的表达增加，表明SC退化到较不成熟的发育状态。总之，我们的结果定义了SC MCT 1对SC代谢和外周神经成熟和衰老的贡献。
Schwann cell (SC)-specific monocarboxylate transporter 1 (MCT1) knockout mice were generated by mating MCT1(f/f) mice with myelin protein zero (P0)-Cre mice. P0-Cre(+/-), MCT1(f/f) 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(f/f) 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.