Dexamethasone is an approved steroid for clinical use to activate or suppress cytokines, chemokines, inflammatory enzymes and adhesion molecules. It enters the brain, by-passing the blood brain barrier, and acts through genomic mechanisms. High levels of dexamethasone are able to induce neuronal cell loss, reduce neurogenesis and cause neuronal dysfunction. The exact mechanisms of steroid, especially the dexamethasone contribute to neuronal damage remain unclear. Therefore, the present study explored the mitochondrial dynamics underlying dexamethasone-induced toxicity of human neuroblastoma SH-SY5Y cells. Neuronal cells treatment with the dexamethasone resulted in a marked decrease in cell proliferation. Dexamethasone-induced neurotoxicity also caused upregulation of mitochondrial fusion and cleaved caspase-3 proteins expression. Mitochondria fusion was found in large proportions of dexamethasone-treated cells. These results suggest that dexamethasone-induced hyperfused mitochondrial structures are associated with a caspase-dependent death process in dexamethasone-induced neurotoxicity. These findings point to the high dosage of dexamethasone as being neurotoxic through impairment of mitochondrial dynamics.
Keywords: Cell Death; Dexamethasone; Mitochondrial dynamics; Mitophagy; Neuron.