Age-dependent changes in translational expression of oligodendrocytes

Most CNS disorders develop with age, along with additional disease-associated etiologies that often involve non-neuronal mechanisms. Oligodendrocytes are crucial for rapid axonal conduction and provide metabolic support to axons, and thus, their altered properties may significantly impact normal functioning of neural networks and degenerative environments in diseases. Here, we document age-related changes in the translational profile of oligodendrocytes with TRAP and RNA-sequencing. The results define the set of mature oligodendrocyte-enriched genes, and bioinformatic analyses suggest that the changes are not limited to rates of myelin synthesis, but extend to myelin composition, as well as declines in membrane trafficking-dependent subcellular activities and creatine synthesis. A striking age-dependent increase of IL-33 may lead to altered patterns of oligodendrocyte and immune cell interactions. Furthermore, marked increases in expression for cation transport and AMPAR subunits with reduced Ca2+ buffering may account for enhanced myelin vulnerability to excitotoxicity in the aged brain.