Persistent neurochemical and behavioral abnormalities in adulthood despite early iron supplementation for perinatal iron deficiency anemia in rats

Abstract

Background: Iron deficiency anemia (IDA) has been associated with altered cognitive, motor, and social-emotional outcomes in human infants. We recently reported that rats with chronic perinatal IDA, had altered regional brain iron, monoamines, and sensorimotor skill emergence during early development.

Objective: To examine the long-term consequences of chronic perinatal IDA on behavior, brain iron and monoamine systems after dietary iron treatment in rats.

Methods: Sixty dams were randomly assigned to iron-sufficient (CN) or low-iron (EID) diets during gestation and lactation. Thereafter, all offspring were fed the iron-sufficient diet, assessed for hematology and behavior after weaning and into adulthood and for brain measures as adults (regional brain iron, monoamines, dopamine and serotonin transporters, and dopamine receptor). Behavioral assessments included sensorimotor function, general activity, response to novelty, spatial alternation, and spatial water maze performance.

Results: Hematology and growth were similar for EID and CN rats by postnatal day 35. In adulthood, EID thalamic iron content was lower. Monoamines, dopamine transporter, and dopamine receptor concentrations did not differ from CN. EID serotonin transporter concentration was reduced in striatum and related regions. EID rats had persisting sensorimotor deficits (delayed vibrissae-evoked forelimb placing, longer sticker removal time, and more imperfect grooming chains), were more hesitant in novel settings, and had poorer spatial water maze performance than CN. General activity and spatial alternation were similar for EID and CN.

Conclusion: Rats that had chronic perinatal IDA showed behavioral impairments that suggest persistent striatal dopamine and hippocampal dysfunction despite normalization of hematology, growth and most brain measures.

Fig. 1

Vibrissae-evoked forelimb placing. Mean percent placing ± S.E.M. *p < 0.001.

Fig. 2

Average sticker touch and removal time in the home cage by diet group. First sticker touch and removal time (time of removal − time of first touch). Mean seconds ± S.E.M. for three trials in the home cage. CN = 24, EID = 21. *p < 0.01.

Fig. 3

Sticker removal time at first trial by setting. Removal time (time of removal − time of first touch) at the first trial in each setting. Mean seconds ± S.E.M. CN = 24, EID = 21. *Diet group: p < 0.05. Diet × setting interaction: p < 0.02.

Fig. 4

Water maze: latency to reach platform. Latency to reach platform in seconds (±S.E.M.) by diet group. CN = 19, EID = 12; day 8 CN = 8, EID = 10. *p < 0.05 days 2–8.

Fig. 5

Water maze: percent path in platform quadrant. Percent path (cm) in the platform quadrant by diet group ± S.E.M. CN = 19, EID = 12; day 8 CN = 8, EID = 10. *p < 0.05 days 3–7.