Melatonin exhibits antioxidant properties in a mouse brain slice model of excitotoxicity

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Clapp-Lilly, Kimberly L. ; Smith, Mark A. ; Perry, George ; Harris, Peggy L. ; Zhu, Xiongwei ; Drew, Kelly L. ; Duffy, Lawrence K. (2002)
  • Publisher: Co-Action Publishing
  • Journal: International Journal of Circumpolar Health (issn: 1797-237X)
  • Related identifiers: doi: 10.3402/ijch.v61i1.17403
  • Subject: antioxidant, brain slices, excitotoxicity, melatonin, stroke

Objectives. Stroke is a major cause of brain injury in Alaska. Since antioxidant levels are decreased in aged brain, the greater predisposition to neuronal death in stroke leading to subsequent neurodegeneration in aged individuals may be related to changes in oxidant balance. We studied the effect of the endogenous antioxidant melatonin on excitotoxic injury resulting from N-methyl- D-aspartate (NMDA)-induced damage by developing an organo-typic mouse brain slice model. Our objective was to inhibit the effects of oxidative stress induced by NMDA in mouse brain slices, using melatonin. Methods. An organotypic mouse brain slice culture was established at PO2 levels maintained between 80 – 100 mm Hg. NMDA, melatonin or both were added to the slices and antioxidant function was determined using the redox active iron assay as well as 8-OHG and HO-1 immunoassays. Results. This slice system allows for better regulation of both NMDA and melatonin concentrations than can be achieved by in vivo studies. Supporting an antioxidant function, melatonin (100 μM) significantly decreased redox active iron, hemexygenase (HO-1) induction and 8-hydroxyguanosine (8-OHG) following NMDA (50-100 μM) insult. However, somewhat surprisingly, high concentrations of melatonin alone (1mM), increased redox active iron levels and HO-1 induction. Conclusions. These results support the hypothesis that melatonin is a neuroprotective antioxidant. Our data also suggest that 1mM melatonin may have detrimental effects.(Int J Circumpolar Health 2002; 61(1):32-40)Keywords: antioxidant, brain slices, excitotoxicity, melatonin, stroke
  • References (17)
    17 references, page 1 of 2

    1. Babu GN and Bawari M: Single microinjection of L-glutamate induces oxidative stress in discrete regions of rat brain. Bichem and Mol Bio Int 1997; 42:1207-17.

    2. Braham B, Forman RE, Stewart EE, Nicholson C, Rice ME: Ascorbate inhibits edema in brain slices. J Neurochem. 2000; 74:1263-1270.

    3. Cabrera J, Reiter RJ,Tan D-X,et al. Melatonin reduces oxidative neurotoxicity due to quinolinic acid: In vitro and in vivo findings, Neuropharm 2000; 39:507-514.

    4. Cazevieille C, Safa R, and Osborne NN. Melatonin protects primary cultures of rat cortical neurons from NMDA excitotixicity and hypoxia/reoxygenation. Brain Research 1997; 768:120-124.

    5. Chan PH. New insights into the role of oxygen radicals in cerebral ischemia. In: Bazan NG, Braquet P, Ginsberg M. Advances in Neurochemistry, volume 7, Neurochemical Correlates of Crebral Ischemia. Plenum Press, NewYork. 1992; 277-294.

    6. Choi DW. Excitoxic Cell Death J. Neurobiology 1992; 23:1261-1276.

    7. Clapp, KL. Investigations into model systems of Neurodegeneration: Organotypic Brain Slice Culture and in vivo microdialysis. Ph.D. Thesis, 2000. Univ of Alaska Fairbanks. 104pp.

    8. Didier M, Bursztajn S, Adamee E, et al. oxidative damage and aging: a hypothesis. J Pineal Research, 1993; 14:151-168.

    23. Reiter RJ,Tan DX, Cabrera J, et al. The oxidant/antioxidant network: role of melatonin. Biol Sign Recept 1999; 8:56-63.

    24. Skene DJ,Vivien-Roels, B, Sparks DL, et al. Daily variation in the concentration of melatonin and 5-hydroxyltryphtol in human pineal gland: effect of age and Alzheimer's disease. Brain Res 1990; 528:170-174.

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