Plasma-Derived MicroRNA hsa-miR-3677-3p Induces Ferroptosis in Neurons by Regulating ABCB8 in Perioperative Neurocognitive Disorders

Perioperative neurocognitive disorders (PND) are prevalent complications in elderly patients following surgery, characterized by cognitive decline and memory impairment. This study investigates the role of plasma-derived exosomal microRNA hsa-miR-3677-3p in regulating ABCB8 and inducing ferroptosis in neuronal cells, contributing to PND. We isolated exosomes 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 indicated that these microRNAs are involved in critical biological processes and pathways related to neuronal function.Further validation demonstrated that hsa-miR-3677-3p directly targets ABCB8, a mitochondrial iron exporter. ABCB8 deficiency triggered iron-dependent oxidative stress, evidenced by decreased antioxidant gene/protein expression, intracellular iron accumulation, elevated malondialdehyde (MDA), reduced GSH/GSSG ratio, and increased MitoPerOx levels. Treatment with the ferroptosis inhibitor Ferrostatin-1 (Fer-1) reversed these effects, restoring mitochondrial function and reducing oxidative damage. Our findings establish exosomal hsa-miR-3677-3p as a key regulator of ABCB8-mediated ferroptosis in neurons, offering novel insights into PND pathogenesis and potential therapeutic strategies.