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Maze learning and motor activity deficits in adult mice induced by iron exposure during a critical postnatal period
A Fredriksson1, N Schröder, P Eriksson
1University of Uppsala, Department of Neuroscience, Psychiatry Ulleråker, Uppsala, Sweden. anders.fredriksson@ullpsyk.uu.se
Insights
Postnatal iron (Fe2+) exposure in mice during critical developmental periods (Days 3-5 and 10-12) caused lasting motor and learning deficits, suggesting potential Parkinsonism symptoms.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Early-life exposure to substances can have profound long-term effects on brain development and function.
- Iron is essential for brain development, but excessive levels can be toxic.
Purpose of the Study:
- To investigate the impact of early-life iron (Fe2+) administration on neurobehavioral development in mice.
- To determine the critical developmental windows for iron-induced neurotoxicity.
Main Methods:
- Newborn mice were administered iron succinate (Fe2+) or vehicle during specific postnatal days (3-5, 10-12, or 19-21).
- Spontaneous motor behavior and radial arm maze learning were assessed at 3 months of age.
- Brain iron content was analyzed in specific regions (basal ganglia, frontal cortex).
Main Results:
- Fe2+ administration during Days 3-5 and 10-12 led to significant motor deficits and impaired learning/memory in the radial arm maze.
- The Days 10-12 treatment group exhibited more pronounced behavioral deficits, indicating higher brain susceptibility during this period.
- Iron accumulation was observed in the basal ganglia but not the frontal cortex in the Fe2+-treated groups.
- Fe2+ administration on Days 19-21 did not result in behavioral alterations.
Conclusions:
- Early-life iron overload during critical postnatal development (Days 3-5 and 10-12) can cause persistent neurobehavioral deficits.
- The basal ganglia appear particularly vulnerable to iron-induced toxicity during these early developmental stages.
- These findings suggest a potential link between early-life iron overload and Parkinsonism-like symptoms, warranting further investigation into iron uptake kinetics and regional distribution.
Abstract:
Newborn mice were administered Fe(2+) (iron succinate: 7.5 mg/kg, b. wt) on either Days 3-5, 10-12 or 19-21, or vehicle (saline) at the same times, postnatally. Spontaneous motor behaviour and radial arm maze learning were tested at the age of 3 months. It was found that mice treated with Fe(2+) during postnatal Days 10-12 were markedly hypokinetic during the 1st 20-min test period and hyperkinetic during the 3rd and final 20-min test period. These mice showed an almost complete lack of habituation of spontaneous motor activity parameters to the test chambers. In the radial arm maze, the Days 10-12 treatment group evidenced significantly both more errors in arm choices and longer latencies to acquire all eight pellets; these mice showed also a severe trial-to-trial retention deficit as indexed by retention quotients. These behavioural deficits were observed also in animals treated with Fe(2+) during postnatal Days 3-5, but the effects were less pronounced, indicating the higher susceptibility of the brain for Fe(2+)-induced damage during Days 10-12 postpartum. Treatment with Fe(2+) on Days 19-21 did not induce behavioural alterations in comparison with its respective control (vehicle) group. Analysis of total brain iron content indicated significantly more iron (microg/g) accumulation in the basal ganglia, but not frontal cortex, of mice from the Days 3-5 and 10-12 Fe(2+) (7.5 mg/kg) treatment groups. The contribution of iron overload during the immediate postnatal to later functional deficits seems to implicate symptoms of Parkinsonism but the kinetics of iron uptake to the brain and its regional distribution at this critical period of development awaits elucidation.
