Changes in the Oligodendrocyte Progenitor Cell Proteome with Ageing

Mol Cell Proteomics. 2020 Aug;19(8):1281-1302. doi: 10.1074/mcp.RA120.002102. Epub 2020 May 20.

Abstract

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.

Keywords: Aging; multiple sclerosis; myelin; neurobiology; neurodegenerative diseases; oligodendrocyte; progenitor cells; regeneration; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Animals, Newborn
  • Biomarkers / metabolism
  • Cell Separation
  • Cholesterol / metabolism
  • Myelin Sheath / metabolism
  • Neurodegenerative Diseases / pathology
  • Oligodendrocyte Precursor Cells / cytology
  • Oligodendrocyte Precursor Cells / metabolism*
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Folding
  • Proteome / metabolism*
  • Proteomics
  • Proteostasis
  • Rats, Sprague-Dawley
  • Reproducibility of Results

Substances

  • Biomarkers
  • Proteome
  • Cholesterol
  • Proteasome Endopeptidase Complex