Neonatal iron potentiates adult MPTP-induced neurodegenerative and functional deficits

The interactive effects of neonatal iron and adult MPTP treatment groups of C57 B1/6 mice were studied through adminustration of iron (Fe2+) 7.5 mg/kg b.w., p.o. or vehicle (saline) on days 10-12 post partum, followed at 3 months of age by administration of either MPTP (2 x 20 or 2 x 40 mg/kg, s.c.) or saline. Neonatal iron administration to mice-induced hypoactivity during the first 20-min period of testing and hyperactivity during the 3rd and final 20-min period for all three parameters of motor activity tested at 4 months of age. MPTP treatment caused a dose-related hypokinesia throughout the 3 x 20-min test periods; in the mice that received both neonatal iron and MPTP severe deficits of motor activity (akinesia) were obtained. Iron treatment impaired the ability of mice to habituate to the novel testing environment and later administration of MPTP potentiated the impairment markedly. Neurochemical analyses of striatal and frontal cortical dopamine (DA) and DA metabolites demonstrated that the depletions were potentiated under conditions of combined neonatal iron and adult MPTP. The analysis of total iron content (mug/g) in brain regions indicated notably elevated levels in the basal ganglia, but not in the frontal cortex, of mice administered Fe2+. Iron-overload combined with MPTP treatment induced functional and neurochemical deficits with interactive consequences beyond a mere additive effect that may have implications for the neurodegenerative process in parkinsonism. (C) 2001 Elsevier Science Ltd. All rights reserved.