@article{c5c1aca13f384f63b43936b41d263b9c,
title = "MCT1 Deletion in Oligodendrocyte Lineage Cells Causes Late-Onset Hypomyelination and Axonal Degeneration",
abstract = "Oligodendrocytes (OLs) are important for myelination and shuttling energy metabolites lactate and pyruvate toward axons through their expression of monocarboxylate transporter 1 (MCT1). Recent studies suggest that loss of OL MCT1 causes axonal degeneration. However, it is unknown how widespread and chronic loss of MCT1 in OLs specifically affects neuronal energy homeostasis with aging. To answer this, MCT1 conditional null mice were generated that allow for OL-specific MCT1 ablation. We observe that MCT1 loss from OL lineage cells is dispensable for normal myelination and axonal energy homeostasis early in life. By contrast, loss of OL lineage MCT1 expression with aging leads to significant axonal degeneration with concomitant hypomyelination. These data support the hypothesis that MCT1 is important for neuronal energy homeostasis in the aging central nervous system (CNS). The reduction in OL MCT1 that occurs with aging may enhance the risk for axonal degeneration and atrophy in neurodegenerative diseases.",
keywords = "adult onset, axonal degeneration, hypomyelination, lactate, metabolic support, monocarboxylate transporter 1, neuron, oligodendrocyte, pyruvate",
author = "Thomas Philips and Mironova, {Yevgeniya A.} and Yan Jouroukhin and Jeannie Chew and Svetlana Vidensky and Farah, {Mohamed H.} and Mikhail Pletnikov and Bergles, {Dwight E.} and Morrison, {Brett M.} and Rothstein, {Jeffrey D.}",
note = "Funding Information: This work was funded by the Muscular Dystrophy Association (MDA, development grant 381190 ) (T.P.), ALS Association (J.D.R.), Department of Defense (J.D.R.), and NIH (J.D.R. and B.M.M.). We thank Carol Cooke for her help with the EM at the Neurology-Peripheral Nerve Division at Johns Hopkins University School of Medicine. We thank members of J.D.R.{\textquoteright}s lab at Johns Hopkins University School of Medicine for helpful discussions. Funding Information: This work was funded by the Muscular Dystrophy Association (MDA, development grant 381190) (T.P.), ALS Association (J.D.R.), Department of Defense (J.D.R.), and NIH (J.D.R. and B.M.M.). We thank Carol Cooke for her help with the EM at the Neurology-Peripheral Nerve Division at Johns Hopkins University School of Medicine. We thank members of J.D.R.?s lab at Johns Hopkins University School of Medicine for helpful discussions. T.P. designed, performed, and analyzed experiments and wrote the manuscript. Y.A.M. performed the electrophysiology experiments and data analysis, which was overseen by D.E.B. Y.J. and M.V.P. assisted with design and data interpretation of the mouse behavioral experiments. S.V. performed the lactate and pyruvate uptake assays. M.H.F. assisted with EM imaging and data analysis. B.M.M. and J.D.R. oversaw the project development, execution, and manuscript writing. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2021",
month = jan,
day = "12",
doi = "10.1016/j.celrep.2020.108610",
language = "English (US)",
volume = "34",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",
}