Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination.

ABSTRACT:

Background

Abnormal lipid accumulation has been recognized as a key element of immune dysregulation in microglia whose dysfunction contributes to neurodegenerative diseases. Microglia play essential roles in the clearance of lipid-rich cellular debris upon myelin damage or demyelination, a common pathogenic event in neuronal disorders. Apolipoprotein E (apoE) plays a pivotal role in brain lipid homeostasis; however, the apoE isoform-dependent mechanisms regulating microglial response upon demyelination remain unclear.

Methods

To determine how apoE isoforms impact microglial response to myelin damage, 2-month-old apoE2-, apoE3-, and apoE4-targeted replacement (TR) mice were fed with normal diet (CTL) or 0.2% cuprizone (CPZ) diet for four weeks to induce demyelination in the b

SUBMITTER: Wang N 

PROVIDER: S-EPMC9682675 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature