title: Melatonin acts as antioxidant and pro-oxidant in an organotypic slice culture model of Alzheimer's disease.
abstract: 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 inmunoreactivity were performed along with morphological analysis for stressed tissue following amyloid-beta (A beta) 1-40 insult. Melatonin (100 microM) significantly reduced the appearance of condensed chromatin, redox active iron, heme-oxygenase-1 induction and 8-hydroxyguanosine immunoreactivity caused by 50 microM A beta. Melatonin also prevented A beta-induced morphological signs of oxidative stress in tissue ultrastructure, 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.
authors.affiliation: Institute of Arctic Biology and Department of Chemistry, University of Alaska Fairbanks, Fairbanks, AK 99775, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Clapp-Lilly
authors.forename: M A
authors.initials: MA
authors.lastname: Smith
authors.forename: G
authors.initials: G
authors.lastname: Perry
authors.forename: P L
authors.initials: PL
authors.lastname: Harris
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: L K
authors.initials: LK
authors.lastname: Duffy
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D008297:Male; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009924:Organ Culture Techniques; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D008565:Membrane Proteins; D016877:Oxidants; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D006151:Guanosine; C046215:8-hydroxyguanosine; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D008550:Melatonin