Amyloid-b neurotoxicity in organotypic culture is attenuated by melatonin: involvement of GSK-3b, tau and neuroinflammation

• Published in: Journal of pineal research 2010-04, Vol.48 (3), p.230-238
• Main Authors: Hoppe, Juliana Bender, Frozza, Rudimar Luiz, Horn, Ana Paula, Comiran, Ricardo Argenta, Bernardi, Andressa, Campos, Maria Martha, Battastini, Ana Maria Oliveira, Salbego, Christianne
• Format: Article
• Language: English
• ISSN: 0742-3098
• DOI: 10.1111/j.1600-079X.2010.00747.x

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by accumulation of extracellular deposits of amyloid-b (Ab) peptide in brain regions that are important for memory and cognition. The buildup of Ab aggregates in the AD is followed by the formation of intracellular neurofibrillary tangles and activation of neuroinflammatory reactions. The present study investigated whether melatonin possesses a neuroprotective effect against Ab-induced toxicity. For this purpose, organotypic hippocampal slices were cultured and exposed to 25 km of Ab25-35 in the absence or in the presence of melatonin (25, 50, or 100 km). In addition, the authors have investigated the involvement of GSK-3b, tau protein, astroglial, and microglial activation, and cytokine levels in the melatonin protection against Ab-induced neurotoxicity. Melatonin prevented the cell damage in hippocampus induced by the exposure to Ab25-35. In addition, melatonin significantly reduced the activation of GSK-3b, the phosphorylation of tau protein, the glial activation and the Ab-induced increase of TNF-a and IL-6 levels. On the basis of these findings, we speculate that melatonin may provide an effective therapeutic strategy for AD, by attenuating Ab-induced phosphorylation of tau protein, and preventing GSK-3b activation and neuroinflammation.