Melatonin attenuates LPS-induced neuroinflammation through modulation of miR-132/miR-124 expression and oxidative stress-related responses in SH-SY5Y cells

Background Age-related decline in melatonin levels has been implicated in neurological disorders. This study aimed to examine how melatonin influences proinflammatory cytokines, oxidative stress-related genes, and the regulation of miRNA-132 and miRNA-124 within an LPS-induced neuroinflammatory cell model. Methods SH-SY5Y cells were co-treated with 5 μg/mL LPS and melatonin (1 or 5 μM) simultaneously for 24 h to investigate the protective effects of melatonin against LPS-induced neuroinflammation. After the 24-h co-treatment period, the levels of proinflammatory cytokines were assessed to confirm neuroinflammation, and BDNF was measured to investigate its potential modulation in response to the LPS-induced inflammatory environment. The expression of miRNA-132 and miR-124-3p was examined using TaqMan real-time PCR. Furthermore, oxidative stress-related gene expression was analyzed using the Human Oxidative Stress Pathway Plus RT 2 Profiler PCR Array. Results Melatonin at both concentrations showed no cytotoxic effects and significantly improved LPS-induced reduction in cell viability. LPS increased IL-6, IL-17, and IL-1β expression and reduced BDNF levels, whereas melatonin co-treatment attenuated inflammatory responses and partially restored BDNF levels. LPS significantly decreased miR-132 and miR-124-3p expression ( p < 0.001), while melatonin increased both miRNAs ( p < 0.001). Inhibition of miR-132 or miR-124-3p enhanced LPS-induced IL-6 and IL-1β expression, whereas melatonin partially reversed these effects. PCR array analysis demonstrated heterogeneous modulation of oxidative stress-related genes involved in antioxidant defense, redox regulation, ROS generation, and inflammatory signaling. Conclusion In this LPS-induced neuroinflammatory model in SH-SY5Y cells, melatonin exerts a protective effect by modulating inflammatory pathways and oxidative stress-related gene expression.