GSE132094
Postweaning iron deficiency in rats alters reelin expression in the nucleus accumbens
Background: Epidemiological research indicates that iron deficiency (ID) in infancy correlates with long-term cognitive impairment and behavioral disturbances, despite therapy. However, the mechanisms underlying these effects are unknown.  Objective: We investigated how ID affected postweaning behavior and monoamine concentration in rat brains to determine whether ID during the juvenile period affected gene expression and synapse formation in the prefrontal cortex (PFC) and nucleus accumbens (NAcc).  Methods: Fischer344/Jcl male rats aged 21–39 days were fed low-iron diets (0.35 mg/kg iron; ID group) or standard AIN-93 G diets (3.5 mg/kg iron; control group). The locomotor activity of male offspring was evaluated by the open field and elevated plus maze tests at ages 8 and 12 weeks. Monoamine concentrations in the PFC, NAcc, caudate-putamen, ventral midbrain, dorsal midbrain, and pons were analyzed. Comprehensive gene expression analysis was performed in the PFC and NAcc at age 13 weeks. Finally, we investigated synaptic density in the PFC and NAcc by synaptophysin immunostaining.  Results: Behavioral tests revealed significant interactions between age and iron consumption for the total distance traveled and the distance traveled in the peripheral area (p < 0.05), indicating that ID during the juvenile period affected hyperactivity and that this persisted to adulthood. At age 13 weeks, the ID group had increased levels of both dopamine and the metabolites of dopamine and serotonin in the NAcc. Comprehensive gene expression analysis and immunostaining showed decreased Reelin gene expression (adjusted p < 0.01) and significantly increased spine density in the NAcc in the ID group compared with the control group (p < 0.01).  Conclusions: ID during the postweaning juvenile period led to long-term hyperactivity, monoamine disturbance in the brain, and downregulation of Reelin expression in the NAcc despite complete iron repletion. Epigenetic modification of Reelin genes may be involved in synaptic plasticity in the NAcc. Overall design: Fischer344/Jcl male rats aged 21-39 days were fed low-iron diets