Novel Cell Models to Study Myelin and Microglia Interactions

Multiple sclerosis (MS) is characterized by demyelination and neuroinflammation, with oxidative stress playing a pivotal role in lesion pathology. This study aimed to investigate the differential cellular responses to myelin debris under varying oxidative states. Myelin oxidation was induced using a Cu-peroxide system, confirmed by elevated TBARS levels and autofluorescence. BV-2 microglia viability remained unaffected by myelin exposure. However, oxidized myelin significantly altered oxidative stress markers, autophagy, and iron metabolism, as evidenced by changes in Sod2, Tfr1, p62, and P-Erk/Erk ratios. Morphological analyses revealed time- and dose-dependent differences in myelin processing, with oxidized myelin leading to distinct phagosome dynamics. Complementary studies using induced microglia-like cells (iMG)-a primary cell culture-confirmed the feasibility of employing oxidized microglia to study microglia activity. The use of iMGs provides a model closer to patient physiology, offering the potential to evaluate individual cellular responses to oxidative damage. This approach could be instrumental in identifying personalized therapeutic strategies by assessing patient-specific microglial behavior in response to myelin debris. These findings highlight the impact of myelin oxidative status on microglial function, advancing the understanding of oxidative stress in MS and paving the way for personalized medicine applications in neuroinflammation.