Monocarboxylate transporter 1 in Schwann cells is critical for maintenance of sensory nerve myelination during aging

Abstract

AbstractSchwann cell (SC)-specific monocarboxylate transporter 1 (MCT1) knockout mice were generated by mating MCT1f/f mice with myelin protein zero (P0)-Cre mice. P0-Cre+/-, MCT1f/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, enlarged node length and reduced mechanical sensitivity were evident in aged P0-Cre+/-, MCT1f/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 (MAG), 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 essential role of SC MCT1 in both SC metabolism and peripheral nerve maturation and aging.Main PointsSC MCT1 deficiency causes hypomyelination of sensory, but not motor, axons during agingEnlarged node length of sensory axons is evident in mutant mouse with SC-specific MCT1 deletionSelective ablation of MCT1 within SCs impairs glycolytic and mitochondrial functionsSC-specific MCT1 deficiency impairs proteins that regulate myelin and lipid metabolism in peripheral nerves