Oligodendrocyte precursor cells facilitate neuronal lysosome release

Oligodendrocyte precursor cells (OPCs) shape brain function through complex mechanisms. We found that OPCs facilitate neuronal lysosome exocytosis by contacting neuronal somata. Reduced number or process branching of OPCs decreased these contacts, accompanied with lysosome accumulation and altered metabolism in neurons, and more senescent neurons with age. In Alzheimer's mouse models, OPC-neuron contacts were fewer, and lysosomes accumulated. Our findings are relevant for preventing aging-related pathologies and treatment of neurodegenerative diseases. Overall design: To investigate the role of OPC-CAV1.2/CAV1.3 in neuronal function, we generated inducible OPC-CAV1.2/CAV1.3 conditional knockout (cKO) mice by cross-breeding NG2-CreERT2 mice, which allow temporal control of OPC-specific gene recombination, with floxed CAV1.2/CAV1.3 mice. mRNA was isolated from OPCs and neurons of the cKO mice and subsequently sent for sequencing.