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^*

^*Corresponding author for this work

Department of Biomedical Sciences

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

41 Citations (Scopus)

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
Pages (from-to)	161-177
Journal	GLIA
Volume	68
Issue number	1
Online published	27 Aug 2019
DOIs	https://doi.org/10.1002/glia.23710
Publication status	Published - Jan 2020

Research Keywords

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

Access Output

10.1002/glia.23710

Other Access Options

Check CityUHK Library

Permanent Link

Right click to copy link

Cite this

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

@article{881da0dd904d4edc8223d65c9b23f70b,

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 = "lactate, MCT1, metabolism, monocarboxylate transporter, myelination, peripheral nerve, Schwann cell, 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.}",

year = "2020",

month = jan,

doi = "10.1002/glia.23710",

language = "English",

volume = "68",

pages = "161--177",

journal = "GLIA",

issn = "0894-1491",

publisher = "John Wiley & Sons",

number = "1",

}

TY - JOUR

T1 - Monocarboxylate transporter 1 in Schwann cells contributes to maintenance of sensory nerve myelination during aging

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

Y1 - 2020/1

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 - lactate

KW - MCT1

KW - metabolism

KW - monocarboxylate transporter

KW - myelination

KW - peripheral nerve

KW - Schwann cell

KW - sensory axons

KW - triacylglycerides

UR - http://www.scopus.com/inward/record.url?scp=85071610134&partnerID=8YFLogxK

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85071610134&origin=recordpage

U2 - 10.1002/glia.23710

DO - 10.1002/glia.23710

M3 - RGC 21 - Publication in refereed journal

C2 - 31453649

SN - 0894-1491

VL - 68

SP - 161

EP - 177

JO - GLIA

JF - GLIA

IS - 1

ER -

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

Abstract

Research Keywords

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Cite this