Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage

Abstract

Oligodendrocyte precursor cells (OPCs) undergo a series of energy-consuming developmental events; however, the uptake and trafficking pathways for their energy metabolites remain unknown. In the present study, we found that 2-NBDG, a fluorescent glucose analog, can be delivered between astrocytes and oligodendrocytes (OLs) through connexin-based gap junction channels but cannot be transferred between astrocytes and OPCs. Instead, connexin hemichannel-mediated glucose uptake supports OPC proliferation, and EtBr uptake or increase of 2-NBDG uptake rate is correlated with intracellular calcium elevation in OPCs, indicating a calcium-dependent activation of connexin hemichannels. Interestingly, deletion of connexin 43 (Cx43) in astrocytes inhibits OPC proliferation by decreasing matrix glucose levels without impacting OPC hemichannel properties, a process that also occurs in corpus callosum from acute brain slices. Thus, dual functions of connexin-based channels contribute to glucose supply in oligodendroglial lineage, which may pave a novel way for energy metabolism-directed oligodendroglial targeted therapies.