Neurobehavioural deficits following postnatal iron overload: II instrumental learning performance

Abstract

Three experiments reporting instrumental learning deficits following postnatal iron overload in rodents are described. In Experiment I, NMRI mice were given different doses of iron succinate (0.0, 3.7 or 37.0 mg Fe 2+ /kg b.w., p.o.) on different postnatal days (PD). In the PD 10-12 group, there were marked disruptions of radial arm maze learning performance in the 37.0 mg Fe 2+ /kg dose group, and to a lesser extent in the 3.7 mg Fe 2+ /kg dose group. In Experiment II, newborn NMRI mice were administered Fe 2+ (7.5 mg/kg, b.w.) at either PD 3-5, PD 10-12, or PD 19-21, or vehicle (saline). Marked deficits in radial arm maze performance were obtained in the mice administered iron during PD 10-12, and to a much lesser extent PD 3-5. In Experiments III and IV, rats were administered two different dose regimes: (i) Experiment III: 2.5, 7.5, 15.0 or 30 mg Fe 2+ /kg b.w., p.o., at PD 10-12, or (ii) Experiment IV: 2.5, 7.5 or 22.5 mg Fe 2+ /kg b.w., p.o., at PD 10-12, followed 3 months later by behavioural testing. All four dose groups in Experiment III demonstrated marked deficits in radial arm maze learning and retention performance but only the 30 mg/kg group showed hypoactivity. In Experiment IV, deficits in inhibitory conditioning were obtained in the 7.5 and 15.0, but not the 2.5, mg/kg dose groups. The analysis of enzymes involved in oxidative stress indicated that: (1) Formation of thiobarbiturate acid reactive species (TBARS) concentration was elevated in the substantia nigra by both the 7.5 and 15.0 mg Fe 2+ /kg doses whereas in the striatum there was a decrease. (2) Superoxide dismutase activity was decreased in a dose-related fashion in the substantia nigra but was elevated in the cerebellum. Iron-overload during the immediate postnatal period incorporating critical synaptogenesis seems detrimental for several aspects of functional and neurobiological development.

Functional Consequences of Iron Overload in Catecholaminergic Interactions: the Youdim Factor

“…Effect of subchronic neuroleptic administration on the functional result of iron overload As demonstrated in several previous studies [75,76,78,[91][92][93][94][95] and confirmed again in the present study, postnatal administration of Fe 2+ (7.5 mg/kg, on Days 10-12) increased the level of iron in the adult mice (Fe-Veh group) to 168% of the Veh-Veh control mice; this concentration is roughly comparable, although at the lower range, to those presented in Fredriksson and Archer [77]. In the Fredriksson et al [92] Study, the analysis of the effects of the 7.5 mg Fe 2+ /kg, administered during postnatal days 10-12 to NMRI mice, upon iron content in the basal ganglia, indicated an increase of 148% in comparison with the associated vehicle control group values.…”