Oxidative memory in microglia: persistent OSI-driven polarization and ıts modulation by mitochondrial dynamics...

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Microglia play crucial roles in neuroinflammation.
• Oxidative stress is implicated in microglial dysfunction.
• Understanding sustained microglial responses to oxidative challenges is vital.

Purpose of the Study:

• To evaluate persistent effects of transient hydrogen peroxide (H₂O₂) on BV2 microglia.
• To compare Mdivi-1's modulation of mitochondrial dynamics with N-acetylcysteine's (NAC) antioxidant buffering.
• To assess the durability of oxidative stress and inflammatory markers.

Main Methods:

• BV2 microglia were exposed to H₂O₂ with or without Mdivi-1 or NAC pretreatment.
• Oxidative stress index (OSI), transcriptional markers (RT-qPCR), cytokines (ELISA), and viability (WST-1) were measured at 2, 24, and 72 hours.
• Focus was on sustained effects at the 72-hour time point.

Main Results:

• Transient H₂O₂ induced a persistent increase in OSI and a proinflammatory profile in BV2 microglia.
• Mdivi-1 improved the microglial phenotype and viability compared to H₂O₂ alone, though OSI was not fully normalized.
• NAC reduced oxidative load but provided less phenotypic recovery than Mdivi-1.

Conclusions:

• A brief oxidative challenge leads to a sustained redox-inflammatory bias in microglia.
• Mdivi-1 demonstrated broader phenotypic recovery than NAC in this experimental model.
• Mechanistic insights into Mdivi-1's effects on mitochondrial dynamics require further investigation.