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 Dastgheyb, Pragney Deme, Xanthe H. Ament, Weiran Chen, Ying Liu, Yun Guan, Michael J Polydefkis, Ahmet Hoke, Norman Haughey, Jeffrey D Rothstein, Brett Morrison

Research output: Contribution to journalArticle

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)
JournalGlia
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Schwann Cells
Maintenance
Peripheral Nerves
Myelin-Associated Glycoprotein
Nerve Growth Factor Receptor
Sphingomyelins
Lipid Metabolism
Knockout Mice

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Monocarboxylate transporter 1 in Schwann cells contributes to maintenance of sensory nerve myelination during aging. / Jha, Mithilesh Kumar; Lee, Youngjin; Russell, Katelyn A.; Yang, Fang; Dastgheyb, Raha; Deme, Pragney; Ament, Xanthe H.; Chen, Weiran; Liu, Ying; Guan, Yun; Polydefkis, Michael J; Hoke, Ahmet; Haughey, Norman; Rothstein, Jeffrey D; Morrison, Brett.

In: Glia, 01.01.2019.

Research output: Contribution to journalArticle

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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.",
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AU - Jha, Mithilesh Kumar

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AU - Ament, Xanthe H.

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AU - Guan, Yun

AU - Polydefkis, Michael J

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AU - Haughey, Norman

AU - Rothstein, Jeffrey D

AU - Morrison, Brett

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