Protective effect of melatonin on β-amyloid-induced apoptosis in rat astroglioma c6 cells and its mechanism

Astrocytosis is a common feature of amyloid plaques. The Aβ–astrocyte interaction produces a detrimental effect on neurons, which may contribute to neurodegeneration in Alzheimer disease (AD). The regulation of astrocyte apoptosis is essential to physiological and pathological processes in the CNS. Melatonin is a potent antioxidant and free radical scavenger. Previously, we showed that melatonin alleviated the learning and memory deficits in the APP 695 transgenic mouse model of AD. In this study, the importance of melatonin in the management of Aβ-induced apoptosis in an astrocyte-like cell is discussed. We found that rat astroglioma C6 cells treated with Aβ25-35 or Aβ1-42 undergo apoptosis and that melatonin pretreatment at 10−5, 10−6, and 10−7 M significantly attenuates Aβ25-35- or Aβ1-42-induced apoptosis. The antiapoptotic effects of melatonin were extremely reproducible and corroborated by multiple quantitative methods, including an MTT cell viability assay, Hoechst 33342 nuclei staining, DNA fragmentation analysis, and flow cytometric analysis. In addition, melatonin effectively suppressed Aβ1-42-induced nitric oxide formation, remarkably prevented Aβ1-40-induced intracellular calcium overload, and significantly alleviated Aβ1-40-induced membrane rigidity. Our results demonstrate that, in addition to the beneficial effects of providing direct antioxidant protection to neurons, melatonin may enhance neuroprotection against Aβ-induced neurotoxicity by promoting the survival of glial cells.