Melatonin acts as antioxidant and prooxidant in an organotypic slice culture model of Alzheimer's disease

An organotypic mouse brain slice culture system of Alzheimer's disease (AD) under low oxygen partial pressures was developed to determine the antioxidant properties of the pineal hormone melatonin in vitro. Assays for biochemical markers of oxidative stress including redox active iron assay, heme-oxygenase-1 and 8-hydroxyguanosine immunoreactivity were performed along with morphological analysis for stressed tissue following amyloid-beta (A beta) 1-40 insult. Melatonin (100 muM) significantly reduced the appearance of condensed chromatin, redox active iron, heme-oxygenase-1 induction and 8-hydroxyguanosine inmunoreactivity caused by 50 muM A beta. Melatonin also prevented A beta -induced morphological signs of oxidative stress in tissue ultrastucture, including edema and dark degenerating profiles as visualized under electron microscope. At elevated concentrations (1 mM), melatonin induced redox active iron and heme-oxgenase-1 immunoreactivity. Thus, while melatonin may be a potential therapeutic agent in the prevention of oxidative stress associated with A beta and AD, it can also induce markers of oxidative stress at millimolar concentrations. NeuroReport 12:1277-1280 (C) 2001 Lippincott Williams & Wilkins.