Recognition memory impairment and brain oxidative stress induced by postnatal iron administration.
Iron accumulation in the brain has been implicated in the pathogenesis of neurodegenerative disorders. It is known that iron catalyses the formation of highly reactive hydroxyl radicals. Recent studies have implicated oxidative damage in memory deficits in rats and humans. The purpose of the present study was to investigate the long-term effects of iron treatment in four different phases of the neonatal period on recognition memory in rats. Additionally, parameters of oxidative stress in cerebral regions related to memory formation were evaluated. Male Wistar rats received vehicle or 10.0 mg/kg of Fe2+ orally at postnatal days 5-7, 12-14, 19-21 or 30-32. Animals given iron at any phase of the neonatal period showed impairments in long-term retention of object recognition memory, although only the group given iron from postnatal days 12-14 showed a complete memory blockade. Iron treatment induced oxidative damage in the brain as assessed by the thiobarbituric acid reactive species assay. Moreover, iron administration increased superoxide production in submitochondrial particles, suggesting impaired mitochondrial function; and there was an increase in superoxide dismutase activity in brain regions susceptible to iron administration. The results show that iron load in the early stages of life induces cognitive impairment possibly by inducing oxidative damage in the brain. These findings are consistent with the view that oxidative stress may be related to the cognitive decline observed in normal ageing.
de Lima
Maria Noemia M
MN
Programa de Pós-Graduação em Gerontologia Biomédica, Instituto de Geriatria e Gerontologia, Pontifícia Universidade Católica do Rio Grande do Sul, 90619-900 Porto Alegre, RS, Brazil.
Polydoro
Manuela
M
Laranja
Daniela C
DC
Bonatto
Fernanda
F
Bromberg
Elke
E
Moreira
José Cláudio F
JC
Dal-Pizzol
Felipe
F
Schröder
Nadja
N
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D007501:Iron / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008928:Mitochondria / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase