Melatonin affects the expression of mitochondrial fission‐fusion proteins in cultured neurons

Abstract

Melatonin (MT) is cytoprotective in different rodent brain ischemia models. MT also increases mitochondrial complex protein I and IV activities, displays antioxidant effects, and stabilizes mitochondrial (mito) membrane potential. However, the effect of MT on mito dynamics has not been examined. Primary rat cortical neurons were isolated from E18 Sprague Dawley fetuses, and were exposed to OGD followed by up 3, 6, or 24 hr reoxygenation. Mito dynamics was investigated by measuring the expression of mito fission protein dynamin‐related peptide 1(Drp1) and fusion proteins mitofusin‐1 and ‐2 (Mfn1, Mfn2) following MT treatment ± OGD. Protective effect of MT treatment was assessed by cell viability assay. We also investigated the effects of MT receptor (MTR) 1 and 2 blocker, Luzindol and MTR3 blocker, prazosin together with MT treatment. MT protected neurons following OGD and this was unaffected by MTR blockers. MT increased mfn‐1 expression in controls, whereas it did not change mfn‐2 expression. MT also increased Drp‐1 expression after OGD that was further increased by both MTRs. In conclusion, MT affords cytoprotection possibly by modulating mitochondrial dynamics in neurons both under normoxic and anoxic conditions. In addition, MTR blockers also influence mitochondrial fission‐fusion proteins; however, they do not alter neuroprotective effect of MT.