Dietary melatonin modulates oxidative rather than inflammatory parameters in the brain
Stephen C. Bondy1, Arezoo Campbell1, Kaizhi Sharman1, Angelica Becaria1, Debomoy Lahiri2, De-Mao Chen2,
Edward Sharman1
1 Department of Community and Environmental Medicine, University of California, Irvine, CA, USA;
2 Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
Received 8 April 2005; accepted 27 May 2005
Correspondence and requests for reprints should be addressed to:
Professor Stephen Bondy
Department of Community and Environmental Medicine
University of California, Irvine, CA, 92697-1825 USA
Tel: (01)9498248077
Fax: ( 01)9498242070
E-mail: scbondy@uci.edu
Abstract
Objectives
Aging is associated with an increase in both inflammation and oxidative damage. Since levels of melatonin are decreased with senescence, we investigated the potential for this neurohormone to reverse age-related changes.
Methodology
Mice, aged 4.5 and 26.5 months, were exposed to dietary melatonin for 65 days. Half of each group of animals was subjected to an inflammatory challenge by i.p. injection of lipopolysaccharide (LPS). Levels of activation of the transcription factor, NF-B, were assayed together with cytokine proteins and their respective mRNAs. Protein carbonylation and nitrosylation were quantitated as indices of oxidative damage, together with levels of amyloid precursor protein and amyloid peptides
Results
The response of NFB to an LPS challenge was elevated in brains of older animals, as were basal levels of mRNA and protein for the inflammatory cytokines, tumor necrosis factor-alpha (TNF) and interleukin 1-alpha (IL-1). However, there was an increase in cortical cytokine mRNA and serum protein levels after the immune challenge. Melatonin lowered the oxidative modification of amino acid residues. Levels of amyloid precursor protein (APP) and amyloid beta peptide (A1-40) were reduced by melatonin in younger but not older mice.
Conclusion
Melatonin may retard some events associated with brain aging only before the onset of the damage. If dietary melatonin is to be used as an anti-aging compound, it is crucial to determine the stage of life necessary for beginning supplementation.
Key Words
Melatonin, brain, aging, inflammation, free radicals, oxidative stress
Categories
Your cart
Authentication