Neonatal iron exposure induces neurobehavioural dysfunctions in adult mice

Excess iron in the brain has been implicated in the pathogenesis of several human neurodegenerative disorders, i.e., Parkinson's and Alzheimer's disea se. The neonatal period is critical for the establishment of normal iron co ntent in the adult brain. In the present study, the long-term neurobehavior al effects of iron exposure during this period were assessed by treating NM RI mice orally with 0.0, 3.7, or 37.0 mg Fe2+/kg body wt on postnatal days 10-12. Spontaneous motor behavior and radial arm maze learning were tested at the age of 3 months. It was found that the mice treated with the higher dose of Fe2+, 37.0 mg/kg body wt, were hypoactive during the first 20 min o f testing but hyperactive during the final 20 min, showing an almost comple te lack of habituation of spontaneous activity in the test chambers. These changes were also seen in animals treated with the lower dose of Fe2+, 3.7 mg/kg body wt, but the effects were less pronounced, indicating a dose-resp onse relationship. In the radial arm maze, the Fe2+ 37.0 mg/kg group eviden ced significantly both more errors in arm choices and longer latencies to a cquire all eight pellets. Both dose groups showed attenuated performance in crements on successive trials. Analysis of brain iron content indicated sig nificantly more total iron (mu g/g) in the basal ganglia, but not frontal c ortex, of the higher, 37 mg/kg, dose group. The knowledge of the long-term effects of iron entering the brain during this critical period of rapid bra in growth is limited. Increased amounts of iron in the brain, especially in the basal ganglia, may contribute to neurodegenerative processes. (C) 1999 Academic Press.