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 disease. The neonatal period is critical for the establishment of normal iron content in the adult brain. In the present study, the long-term neurobehavioral effects of iron exposure during this period were assessed by treating NMRI mice orally with 0.0, 3.7, or 37.0 mg Fe(2+)/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 Fe(2+), 37.0 mg/kg body wt, were hypoactive during the first 20 min of testing but hyperactive during the final 20 min, showing an almost complete lack of habituation of spontaneous activity in the test chambers. These changes were also seen in animals treated with the lower dose of Fe(2+), 3.7 mg/kg body wt, but the effects were less pronounced, indicating a dose-response relationship. In the radial arm maze, the Fe(2+) 37.0 mg/kg group evidenced significantly both more errors in arm choices and longer latencies to acquire all eight pellets. Both dose groups showed attenuated performance increments on successive trials. Analysis of brain iron content indicated significantly more total iron (microgram/g) in the basal ganglia, but not frontal cortex, 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 brain growth is limited. Increased amounts of iron in the brain, especially in the basal ganglia, may contribute to neurodegenerative processes.
Fredriksson
A
A
Department of Neuroscience, University of Uppsala, Uppsala, S-750 17, Sweden.
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*; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000737:chemistry; D005260:Female; D007501:Iron / Q000032:analysis / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009420:Nervous System / Q000187:drug effects*; D011247:Pregnancy; D013997:Time Factors
D007501:Iron