title: Age-related differences in the response of the brain to dietary melatonin.
abstract: The aged brain is prone to excessive levels of immune activity, not initiated by an acute response to an extrinsic agent. While dietary melatonin is reported to attenuate the extent of expression of proinflammatory genes, little is known about the extent to which these changes can be translated into altered levels of corresponding proteins. The baseline levels of the proinflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-1 alpha, were greater in older (~29 months old) compared to younger (~7 months old) mouse brains. Acute (3 h) exposure to lipopolysaccharide (LPS) induced activation of nuclear factor kappa B (NF-κB), but not inflammatory cytokines in the brain. The serum level of TNF-α was increased after LPS injection, indicating a systemic immune response to the bacterial cell wall component. Dietary melatonin (40 ppm for 9.3 weeks) did not prevent LPS-induced changes in younger animals but caused an increased systemic TNF-α response in older mice. Melatonin did reduce markers of carbonyl formation in brain proteins of young animals and nitrosylative damage to peptide-bound amino acid residues, in the brains of older animals. Acute LPS challenge did not significantly affect these oxidative markers. Thus, despite lack of clear evidence of attenuation of the NF-κB-cytokine inflammatory trajectory within the CNS by melatonin, this agent did show a protective effect against free radical-initiated injury to amino acid residues within proteins. The results illustrate that previously reported changes in gene expression following melatonin treatment need not be closely paralleled by corresponding changes in protein content.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, 91766-1854, USA, acampbell@westernu.edu.
authors.forename: Arezoo
authors.initials: A
authors.lastname: Campbell
authors.forename: Edward
authors.initials: E
authors.lastname: Sharman
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Bondy
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression; D007124:Immunoenzyme Techniques; D053582:Interleukin-1alpha / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053582:Interleukin-1alpha; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D008550:Melatonin