Neonatal iron treatment increases apoptotic markers in hippocampal and cortical areas of adult rats.
Oxidative stress, cellular damage, and neuronal apoptosis are believed to underlie the progressive cognitive decline that accompanies natural aging and to be exacerbated in neurodegenerative diseases. Over the years, we have consistently demonstrated that iron neonatal treatment induces oxidative stress and memory deficits in adult rats, but the mechanisms underlying these effects remained undefined. The purpose of this study was to examine whether neonatal iron overload was associated with apoptotic cell death in adult and old rats. We analyzed Par-4 and caspase-3 immunoreactivity in specific brain areas including the hippocampus CA1, CA3 and dentate gyrus (DG), the adjacent cortex and the striatum in adult (3 months-old) and aged (24 months-old) rats from control (vehicle-treated) and neonatally iron-treated groups. Neonatal iron treatment consisted of a daily oral administration of 10 mg/kg of Fe(+2), for three consecutive days, from post-natal 12-14. Control aged animals showed increased levels of both markers when compared to untreated adult animals. When adults were compared, iron-treated animals presented significantly higher Par-4 and caspase-3 immunoreactivities in CA1, CA3 and cortex. In the DG, this effect was statistically significant only for Par-4. Interestingly, when control and iron-treated aged animals were compared, a significant decrease in both apoptotic markers was observed in the later groups in the same areas. These results may be interpreted as an acceleration of aging progressive damages caused by iron overload and may contribute to a better understanding of the damaging potential of iron accumulation to brain function and the resulting increased susceptibility to neurodegeneration.
Miwa
Clivia Pazin
CP
Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, Av. Ipiranga, 6681 Prédio 12D, Sala 340, 90619-900 Porto Alegre, RS, Brazil.
de Lima
Maria Noêmia Martins
MN
Scalco
Felipe
F
Vedana
Gustavo
G
Mattos
Raquel
R
Fernandez
Liana Lisboa
LL
Hilbig
Arlete
A
Schröder
Nadja
N
Vianna
Monica R M
MR
D000375:Aging / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000096:biosynthesis; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D019266:Iron, Dietary / Q000008:administration & dosage* / Q000633:toxicity; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D051017:Apoptosis Regulatory Proteins; D019266:Iron, Dietary; C101296:prostate apoptosis response-4 protein; C505410:Casp3 protein, rat; D053148:Caspase 3