Changes in the Oligodendrocyte Progenitor Cell Proteome with Ageing

Oligodendrocyte progenitor cell (OPC)-mediated remyelination declines with ageing. We have determined the proteome of neonatal, young and aged rat OPCs using quantitative MS-proteomics. We identify increases in myelin proteins as well as changes in inflammation, cholesterol biosynthesis and protein homeostasis pathways in OPCs with ageing. These data provide a resource to study age-associated changes in OPCs that may contribute to the age-related decrease in oligodendrogliogenesis. [Display omitted] Highlights •Quantitative proteome of neonatal, young, and aged OPCs.•50% of the proteome is differentially expressed between neonatal and adult OPCs.•Myelin proteins are increased, and cholesterol synthesis proteins decreased with age.•Proteins associated with other neurodegenerative diseases are increased in aged OPCs. Following central nervous system (CNS) demyelination, adult oligodendrocyte progenitor cells (OPCs) can differentiate into new myelin-forming oligodendrocytes in a regenerative process called remyelination. Although remyelination is very efficient in young adults, its efficiency declines progressively with ageing. Here we performed proteomic analysis of OPCs freshly isolated from the brains of neonate, young and aged female rats. Approximately 50% of the proteins are expressed at different levels in OPCs from neonates compared with their adult counterparts. The amount of myelin-associated proteins, and proteins associated with oxidative phosphorylation, inflammatory responses and actin cytoskeletal organization increased with age, whereas cholesterol-biosynthesis, transcription factors and cell cycle proteins decreased. Our experiments provide the first ageing OPC proteome, revealing the distinct features of OPCs at different ages. These studies provide new insights into why remyelination efficiency declines with ageing and potential roles for aged OPCs in other neurodegenerative diseases.