Oligodendroglial fatty acid metabolism as a central nervous system energy reserve

ABSTRACT: Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. Here, we addressed the question whether oligodendroglial lipid metabolism can provide an energy reserve in white matter tracts. Among other approaches including microscopy and electrophysiology applied to acutely isolated optic nerves from young adult mice used as a model system, we also employed quantitative proteome analysis to study alterations of the whole optic nerve proteome upon glucose deprivation. We compared optic nerve fractions from two different low-glucose incubation conditions (16 h in 0 mM glucose/10 mM sucrose or 24 h in 1 mM glucose/9 mM sucrose) with those from the respective control conditions in regular medium (10 mM glucose/0 mM sucrose). Optic nerve fractions from five animals per condition were processed with replicate digestion, resulting in two technical replicates per biological replicate and thus in a total of 20 LC-MS runs to be compared per individual experiment. 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 optic nerve proteome. Label-free protein quantification revealed a non-significant trend toward higher myelin protein abundance, a reduced abundance of some glycolytic enzymes, an increased abundance of fatty acid binding proteins and enzymes of fatty acid metabolism, as well as a higher steady-state level of some autophagy-related proteins. Taken together, our study indicates that ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism, and that the imbalance of myelin synthesis and degradation can underlie unexplained myelin thinning in aging and disease.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Oligodendrocyte, Optic Nerve

SUBMITTER: Olaf Jahn  

LAB HEAD: Prof. Dr. Olaf Jahn

PROVIDER: PXD053960 | Pride | 2024-07-16

REPOSITORIES: Pride