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.
This study was aimed to investigate neuropathological changes in adult and aged rats subjected to supplementary iron administration in a critical postnatal period to study the contribution of environmental risk factors to the pathogenesis of neurodegenerative disorders. Ten rats received a single daily oral administration of iron (10 mg/kg) between 12th and 14th post-natal days; nine rats received vehicle (sorbitol 5% in water) in the same period. Five iron-treated and three sorbitol-treated rats were killed at the age of 3 months while five iron-treated and six sorbitol-treated rats were killed at age of 24 months and their brains processed for immunohistochemistry. Increased astrocytosis, revealed by densitometry of GFAP-immunoreactive astrocytes, was found in aged (24 months) iron-treated rats in the substantia nigra and striatum and in the hippocampus of adult (3 months) iron-treated rats when compared to age-matching controls. Decreased densitometry of neurons, revealed by neuronal nucleus immunohistochemistry, was found in aged (24 months) iron-treated rats in substantia nigra and striatum when compared to age-matching controls. These findings suggest that transient dietary iron supplementation during the neonatal period is associated to cellular imprinting in the brain later in life.
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