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

doi:10.1002/glia.23710

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	161-177
Number of pages	17
Journal	Glia
Volume	68
Issue number	1
DOIs	https://doi.org/10.1002/glia.23710
State	Published - 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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10.1002/glia.23710

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Jha, M. K., Lee, Y., Russell, K. A., Yang, F., Dastgheyb, R. M., Deme, P., Ament, X. H., Chen, W., Liu, Y., Guan, Y., Polydefkis, M. J., Hoke, A., Haughey, N. J., Rothstein, J. D., & Morrison, B. M. (2020). Monocarboxylate transporter 1 in Schwann cells contributes to maintenance of sensory nerve myelination during aging. Glia, 68(1), 161-177. https://doi.org/10.1002/glia.23710

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title = "Monocarboxylate transporter 1 in Schwann cells contributes to maintenance of sensory nerve myelination during aging",

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.",

keywords = "MCT1, Schwann cell, lactate, metabolism, monocarboxylate transporter, myelination, peripheral nerve, sensory axons, triacylglycerides",

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

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year = "2020",

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doi = "10.1002/glia.23710",

language = "English (US)",

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AU - Jha, Mithilesh Kumar

AU - Lee, Youngjin

AU - Russell, Katelyn A.

AU - Yang, Fang

AU - Dastgheyb, Raha M.

AU - Deme, Pragney

AU - Ament, Xanthe H.

AU - Chen, Weiran

AU - Liu, Ying

AU - Guan, Yun

AU - Polydefkis, Michael J.

AU - Hoke, Ahmet

AU - Haughey, Norman J.

AU - Rothstein, Jeffrey D.

AU - Morrison, Brett M.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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.

AB - 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.

KW - MCT1

KW - Schwann cell

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KW - myelination

KW - peripheral nerve

KW - sensory axons

KW - triacylglycerides

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

Abstract

Keywords

ASJC Scopus subject areas

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