Neuroprotective effect of melatonin on soluble Aβ 1-42 -induced cortical neurodegeneration via Reelin-Dab1 signaling pathway.

Objective: Soluble A beta(1-42) oligomers play a vital role in the development and pathogenesis of Alzheimer's disease (AD). Melatonin could delay the progress of AD through multiple mechanisms. Reelin-Dab1 signaling plays an important role in AD, including neuronal function and synaptic plasticity. However, whether melatonin could exert its neuroprotective function against soluble A beta(1-42)-induced neurotoxicity during AD development through regulating Reelin-Dab1 signaling remains poorly understood. Methods: AD rat model was established by soluble A beta(1-42) repeated intracerebroventricular injection. Using immunohistochemistry and Western blot analyses, the effect of melatonin on synaptic plasticity, neuritic degeneration, and astrocyte activation was investigated in cerebral cortex. Meanwhile, the expression of Reelin and Dab1 was also examined in cerebral cortex. In our in vitro study, Reelin-Dab1 signaling was inhibited by Reelin antibody, and neuroprotective effect of melatonin against A beta(1-42) was further determined. Results: Melatonin ameliorated the neurotoxiciy and astrocyte activation induced by A beta(1-42) in the cerebral cortex. Melatonin also blocked the reduction in Reelin and Dab1 expression induced by A beta(1-42). Using in vitro study, Reelin inactivation completely abolished the protective effect of melatonin against A beta(1-42)-induced neurotoxicity. Discussion: Melatonin might play its neuroprotective role against A beta(1-42) through mediating Reelin-Dab1 signaling pathway. Melatonin could be a safe and remarkable therapeutic candidate for AD and other aged-associated neurodegenerative diseases.