Lipidomic Analysis Reveals Differences in the Extent of Remyelination in the Brain and Spinal Cord

During demyelination, lipid-rich
myelin debris is released in the
central nervous system (CNS) and must be phagocytosed and processed
before new myelin can form. Although myelin comprises over 70% lipids,
relatively little is known about how the CNS lipidome changes during
demyelination and remyelination. In this study, we obtained a longitudinal
lipidomic profile of the brain, spinal cord, and serum using a genetic
mouse model of demyelination, known as Plp1-iCKO-Myrf. The mass spectrometry data is available at the Metabolomics
Workbench, where it has been assigned Study ID ST002958. This model
has distinct phases of demyelination and remyelination over the course
of 24 weeks, in which loss of motor function peaks during demyelination.
Using principal component analysis (PCA) and volcano plots, we have
demonstrated that the brain and spinal cord have different remyelination
capabilities and that this is reflected in different lipidomic profiles
over time. We observed that plasmalogens (ether-linked phosphatidylserine
and ether-linked phosphatidylcholine) were elevated specifically during
the early stages of active demyelination. In addition, we identified
lipids in the brain that were altered when mice were treated with
a remyelinating drug, which may be CNS biomarkers of remyelination.
The results of this study provide new insights into how the lipidome
changes in response to demyelination, which will enable future studies
to elucidate mechanisms of lipid regulation during demyelination and
remyelination.