Monocarboxylate transporter 1 in Schwann cells contributes to maintenance of sensory nerve myelination during aging

Mithilesh Kumar Jha, Youngjin Lee, Katelyn A. Russell, Fang Yang, Raha M. Dastgheyb, Pragney Deme, Xanthe H. Ament, Weiran Chen, Ying Liu, Yun Guan, Michael J. Polydefkis, Ahmet Hoke, Norman J. Haughey, Jeffrey D. Rothstein, Brett M. Morrison

Research output: Contribution to journalArticlepeer-review

Abstract

Schwann 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, reduced mechanical sensitivity is 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, 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.

Original languageEnglish (US)
Pages (from-to)161-177
Number of pages17
JournalGlia
Volume68
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • MCT1
  • Schwann cell
  • lactate
  • metabolism
  • monocarboxylate transporter
  • myelination
  • peripheral nerve
  • sensory axons
  • triacylglycerides

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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