Melatonin exhibits antioxidant properties in a mouse brain slice model of excitotoxicity.
OBJECTIVE
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 organotypic 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 microM) significantly decreased redox active iron, heme-oxygenase (HO-1) induction and 8-hydroxyguanosine (8-OHG) following NMDA (50-100 microM) insult. However, somewhat surprisingly, high concentrations of melatonin alone (1 mM), 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 1 mM melatonin may have detrimental effects.
Clapp-Lilly
Kimberly L
KL
Institute of Arctic Biology and Department of Chemistry and Biochemistry, University of Alaska Fairbanks, 99775, USA.
Smith
Mark A
MA
Perry
George
G
Harris
Peggy L
PL
Zhu
Xiongwei
X
Drew
Kelly L
KL
Duffy
Lawrence K
LK
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D066298:In Vitro Techniques; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity*; D020521:Stroke / Q000503:physiopathology
D000975:Antioxidants; D018691:Excitatory Amino Acid Antagonists; D016202:N-Methylaspartate; D008550:Melatonin