Monocarboxylate Transporter 1 and the Vulnerability of Oligodendrocyte Lineage Cells to Metabolic Stresses

Aims: Oligodendrocytes, especially oligodendrocyte precursor cells, are known to be sensitive to hypoxic and metabolic stresses. Vulnerability of oligodendrocytes is considered a contributing factor to white matter dysfunction. However, little is known about the energy processing characteristics of oligodendrocyte lineage cells under basal and metabolic stress conditions. The aim of this study was to identify the energy requirements and cellular responses of oligodendrocytes at different developmental stages.

Methods: We compared the metabolic stress responses between myelinating oligodendrocytes (OLs) and oligodendrocyte precursor cells (OPCs). Differential regulation of cellular response was also investigated.

Results: We found that, following cerebral ischemia, monocarboxylate transporter 1 (MCT1) expression was upregulated in the peri-infarct striatum but not in the cortex of the brain. In vitro ischemia models were used to induce oligodendrocyte stress as well. An increase in MCT1 expression was detected in OPCs after a mild oxygen-glucose deprivation. Double-labeled immunohistochemical analysis revealed that OPCs and OLs responded differently to metabolic stresses and that the susceptibility to metabolic stresses of OPCs and OLs was associated with their distinct expression profiles of MCT1.

Conclusion: Taken together, this study shows that MCT1 plays a role in the responses of OPCs and OLs to metabolic and ischemic stresses and suggests that redistribution of energy substrates is a determinant in white matter injury.