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Memory deficits in adult rats following postnatal iron administration
N Schröder1, A Fredriksson, M R Vianna
1Departamento de Bioquimica, UFRGS, Porto Alegre, Brazil.
Insights
Postnatal iron (Fe(2+)) administration in rats impaired memory and motor functions, with lasting detrimental effects observed across multiple cognitive tests. Higher iron doses increased iron levels in the substantia nigra, correlating with behavioral deficits.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Early-life exposure to substances can have long-lasting neurodevelopmental consequences.
- Iron is essential for brain development, but excessive levels can be toxic.
Purpose of the Study:
- To investigate the long-term effects of postnatal iron (Fe(2+)) administration on memory and motor behavior in rats.
- To determine dose-dependent effects and identify brain regions affected by iron exposure.
Main Methods:
- Wistar rats received varying doses of Fe(2+) or vehicle on postnatal days 10-12.
- Behavioral testing at 3 months included open-field, radial arm maze, and inhibitory avoidance (IA) tasks.
- Iron content analysis of brain tissue, specifically the substantia nigra.
Main Results:
- Fe(2+) administration led to deficits in radial arm maze acquisition and retention, and impaired IA retention in a dose-dependent manner.
- Motor activity was reduced only at the highest Fe(2+) dose in the open-field test.
- Significant iron accumulation was found in the substantia nigra for higher Fe(2+) doses.
Conclusions:
- Postnatal iron administration induces persistent detrimental effects on learning and memory, regardless of reinforcement type.
- Iron accumulation in the substantia nigra may underlie observed behavioral impairments.
- These findings highlight potential risks of early-life iron overload on neurodevelopment.
Abstract:
Two experiments investigated the effects of Fe(2+), administered postnatally to rat pups on days 10-12, upon tests of memory performance and motor behaviour. In experiment I, Wistar rat pups were administered Fe(2+) at doses of either 2.5, 7.5, 15.0 or 30.0 mg/kg, or vehicle, postnatally, and tested in the open-field at 3 months of age, followed 6 weeks later by testing in the radial arm maze. In the open-field test, only the 30.0 mg/kg Fe(2+) group showed a significantly decreased number of ambulations, but not rearings. In the radial arm maze, all four dose groups, demonstrated deficits in acquisition performance from test days 3 to 5. Retention quotients confirmed the cognitive deficits over all four Fe(2+) groups. In experiment II, rats were administered either 2.5, 7.5 or 22.5 mg Fe(2+) per kg, or vehicle, postnatally, and tested in the inhibitory avoidance (IA) conditioning and retention test at 3 months of age. In the IA conditioning test, groups were either given five 10-min preexposures to the test chamber (preexposed) or simply moved to another cage (non-preexposed). IA retention was blocked in non-preexposed rats administered 7.5 and 22.5 mg Fe(2+) per kg whereas in preexposed rats the 7.5 mg/kg group did not differ from the control (vehicle) group, although the preexposed control group showed significantly better retention than the non-preexposed control group. Postnatal iron administration appears to induce long-lasting detrimental effects upon performance of both appetitively and negatively reinforced tests of memory. Analysis of iron content indicated significant increases in the substantia nigra of the 7.5, 15.0 and 30.0 mg/kg dose groups, but not in the 2.5 mg/kg dose group. Postnatal iron administration appears to induce far-reaching effects upon the performance of certain learned behaviours.