Sub-Chronic 30 mg/kg Iron Treatment Induces Spatial Cognition Impairment and Brain Oxidative Stress in Wistar Rats.

Abstract

Iron overload has been shown to have deleterious effects in the brain through the formation of reactive oxygen species, which ultimately may contribute to neurodegenerative disorders. Accordingly, rodent studies have indicated that systemic administration of iron produces excess iron in the brain and results in behavioral and cognitive deficits. To what extent cognitive abilities are affected and which neurobiological mechanisms underlie those deficits remain to be more fully characterized. In the present study, we looked at the effects of a 30 mg/kg iron sub-chronic treatment on cognitive abilities in two hippocampal-dependent spatial tasks (place navigation, spatial/non-spatial object recognition), in relation with iron content and oxidative stress biomarkers (MDA, SOD, CAT) in the cerebellum, hippocampus, prefrontal cortex and striatum, four brain areas known to be involved in the processing of spatial information. Iron-treated rats were impaired in acquisition and retention of the platform location in the navigation task and in the spatial/non-spatial object recognition task. Iron content and MDA were found to be increased in the four brain regions of interest, but activity of the antioxidant enzymes was not modified. The results indicate that the ability of rats to process spatial information whether in place navigation or spontaneous object spatial/non-spatial recognition is disrupted following a 30 mg/kg sub-chronic treatment. The deficits are hypothesized to result from iron excess-induced oxidative stress in the network of brain areas involved in the processing of spatial information.