Plasma-Derived Exosomal hsa-miR-3677-3p Induces Ferroptosis in Neurons by Targeting ABCB8 in Perioperative Neurocognitive Disorders After Prostate Surgery.

Perioperative neurocognitive disorders (PND) are prevalent complications in elderly patients following surgery, characterized by cognitive decline and memory impairment. This study investigates the contribution of plasma-derived exosomal microRNA hsa-miR-3677-3p to PND pathogenesis via ABCB8 regulation and subsequent induction of neuronal ferroptosis. Exosomes were isolated from plasma of patients with delayed neurocognitive recovery (dNCR) and non-dNCR patients. Characterization confirmed successful exosome isolation, revealing distinct microRNA profiles between the two groups. MicroRNA sequencing identified 69 differentially expressed microRNAs, with hsa-miR-3677-3p significantly upregulated in dNCR patients. Functional enrichment analysis implicated these microRNAs in mitochondrial function and nervous system development. In vitro overexpression of hsa-miR-3677-3p mimicked the pathological phenotype, leading to downregulation of ABCB8, which resulted in iron dyshomeostasis and oxidative stress, marked by reduced antioxidant capacity, intracellular iron accumulation, elevated malondialdehyde (MDA), a decreased glutathione/glutathione disulfide (GSH/GSSG) ratio, and increased mitochondrial lipid peroxidation (MitoPerOx). Treatment with the ferroptosis inhibitor Ferrostatin-1 (Fer-1) attenuated these alterations, restoring mitochondrial function and reducing oxidative damage. Taken together, our findings indicate that exosomal hsa-miR-3677-3p modulates ABCB8-mediated ferroptosis in neurons, highlighting a novel insight into PND pathogenesis and potential therapeutic strategies.