Transcriptome Analysis Unveils That Exosomes Derived from M1-Polarized Microglia Induce Ferroptosis of Neuronal Cells

Microglia play a vital role in neurodegenerative diseases. However, the effects of microglia-derived exosomes on neuronal cells are poorly understood. This study aimed to explore the role of M1-polarized microglia exosomes in neuronal cells by transcriptome analysis. Exosomes isolated from resting M0-phenotype BV2 (M0-BV2) microglia and M1-polarized BV2 (M1-BV2) microglia were analyzed using high-throughput sequencing of the transcriptome. Differentially expressed genes (DEGs) between the two types of exosomes were identified by analyzing the sequencing data. The biological functions and pathways regulated by the identified DEGs were then identified using bioinformatics analyses. Finally, we evaluated the effects of exosomes on neuronal cells by coculturing M0-BV2 and M1-BV2 exosomes with primary neuronal cells. Enrichment analyses revealed that DEGs were significantly enriched in the ferroptosis pathway (p = 0.0137). M0-BV2 exosomes had no distinct effects on ferroptosis in neuronal cells, whereas M1-BV2 exosomes significantly reduced ferroptosis suppressor proteins (GPX4, SLC7A11, and FTH1) and elevated the levels of intracellular and mitochondrial ferrous iron and lipid peroxidation in neuronal cells. Polarized M1-BV2 microglia exosomes can induce ferroptosis in neuronal cells, thereby aggravating neuronal damage. Taken together, these findings enhance knowledge of the pathogenesis of neurological disorders and suggest potential therapeutic targets against neurodegenerative diseases.