Maze learning and motor activity deficits in adult mice induced by iron exposure during a critical postnatal period.
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.
Fredriksson
A
A
University of Uppsala, Department of Neuroscience, Psychiatry Ulleråker, Uppsala, Sweden. anders.fredriksson@ullpsyk.uu.se
Schröder
N
N
Eriksson
P
P
Izquierdo
I
I
Archer
T
T
D000818:Animals; D000831:Animals, Newborn; D001479:Basal Ganglia / Q000737:chemistry; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005296:Ferrous Compounds; D005625:Frontal Lobe / Q000737:chemistry; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D006948:Hyperkinesis / Q000139:chemically induced; D018476:Hypokinesia / Q000139:chemically induced; D007501:Iron / Q000032:analysis / Q000633:toxicity*; D019190:Iron Overload / Q000139:chemically induced / Q000150:complications*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced; D051379:Mice; D008815:Mice, Inbred Strains / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects
D005296:Ferrous Compounds; C022943:ferrous succinate; D007501:Iron