Astrocytosis is a common feature of
amyloid plaques. The Abeta-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 Abeta-induced apoptosis in an astrocyte-like cell is discussed. We found that rat
astroglioma C6 cells treated with
Abeta25-35 or Abeta1-42 undergo apoptosis and that
melatonin pretreatment
at 10(-5), 10(-6), and 10(-7) M significantly attenuates Abeta25-35- or Abeta1-42-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 Abeta1-42-induced
nitric oxide formation, remarkably prevented Abeta1-40-induced intracellular
calcium overload, and significantly alleviated Abeta1-40-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 Abeta-induced neurotoxicity by promoting the survival of glial cells.