MCT1 Deletion in Oligodendrocyte Lineage Cells Causes Late-Onset Hypomyelination and Axonal Degeneration

Thomas Philips, Yevgeniya A. Mironova, Yan Jouroukhin, Jeannie Chew, Svetlana Vidensky, Mohamed H. Farah, Mikhail V. Pletnikov, Dwight E. Bergles, Brett M. Morrison, Jeffrey D. Rothstein

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number108610
JournalCell Reports
Volume34
Issue number2
DOIs
StatePublished - Jan 12 2021

Keywords

  • adult onset
  • axonal degeneration
  • hypomyelination
  • lactate
  • metabolic support
  • monocarboxylate transporter 1
  • neuron
  • oligodendrocyte
  • pyruvate

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'MCT1 Deletion in Oligodendrocyte Lineage Cells Causes Late-Onset Hypomyelination and Axonal Degeneration'. Together they form a unique fingerprint.

Cite this