Reversal of biochemical and behavioral parameters of brain aging by melatonin and acetyl L-carnitine.
The potential utility of dietary supplementation in order to prevent some of the oxidative and inflammatory changes occurring in the brain with age, has been studied. The cerebral cortex of 27-month-old male B6C3F1 mice had elevated levels of nitric oxide synthase 1 (EC 1.14.13.39) (nNOS) and peptide nitrotyrosine relative to cortices of younger (4-month-old) animals. After 25-month-old mice received basal diet together with 300 mg/l acetyl L-carnitine in the drinking water for 8 weeks, these levels were fully restored to those found in younger animals. A partial restoration was found when old animals received basal diet supplemented with 200 ppm melatonin in the diet. Levels of mRNA (messenger RNA) for nNOS were unchanged following these treatments implying translational regulation of nNOS activity. Behavioral indices indicative of exploratory behavior were also depressed in aged animals. Dietary supplementation with melatonin or acetyl L-carnitine partially reversed these changes. These findings suggest that dietary supplementation cannot merely arrest but indeed reverse some age-related increases in markers of oxidative and inflammatory events occurring with the cortex.
Sharman
Edward H
EH
Center for Occupational and Environmental Health, Department of Community and Environmental Medicine, University of California Irvine, Irvine, CA 92697-1825, USA.
Vaziri
Nosratola D
ND
Ni
Zhenmin
Z
Sharman
Kaizhi G
KG
Bondy
S C
SC
D000108:Acetylcarnitine / Q000494:pharmacology*; D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D004660:Encephalitis / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D000108:Acetylcarnitine; D019001:Nitric Oxide Synthase; D008550:Melatonin