Developmental maturation but no sex-dependent divergence of the murine CNS myelin proteome

ABSTRACT: To assess whether the CNS myelin proteome varies within the same species, we used quantitative mass spectrometry to compare myelin purified from mouse brains at three developmental timepoints (P18, P75, 6 months), brains of male and female mice, and four CNS regions (cortex, corpus callosum, optic nerve, spinal cord). We utilized a data-independent acquisition (DIA) workflow with alternating low and elevated energy (MSE) and an ion mobility-enhanced version thereof (referred to as UDMSE) to achieve both, a correct quantification of exceptionally abundant myelin proteins and a comprehensive coverage of the myelin proteome. Label-free protein quantification revealed that the myelin protein composition matures between P18 and P75, and remains largely similar up to 6 months. Proteins with decreasing abundance included cytoskeleton-associated proteins (regulating sheath growth and wrapping), whereas proteins with increasing abundance included all subunits of the septin filament (stabilizing mature myelin), and potentially protective proteins. Among the latter was quinoid dihydropteridine reductase (QDPR), which emerges as a highly specific marker for mature oligodendrocytes and myelin. Conversely, female and male mice display essentially similar myelin proteomes and the myelin-enriched fractions from the four CNS regions mainly differ by the abundance of HCN2-channels in spinal cord myelin as a requirement for particularly long sheaths, apart from the extent of contaminating mitochondrial and synaptic proteins.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Spinal Cord, Oligodendrocyte, Myelin Sheath, Optic Nerve

SUBMITTER: Olaf Jahn  

LAB HEAD: Olaf Jahn

PROVIDER: PXD053062 | Pride | 2024-08-27

REPOSITORIES: Pride