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Effect of dietary iron loading on recognition memory in growing rats.

Han M, Kim J - PLoS ONE (2015)

Bottom Line: While nutritional and neurobehavioral problems are associated with both iron deficiency during growth and overload in the elderly, the effect of iron loading in growing ages on neurobehavioral performance has not been fully explored.These results support the idea that iron is essential for learning and memory and further reveal that iron supplementation during developmental and rapidly growing periods of life improves memory performance.Our investigation also demonstrates that both cholinergic and glutamatergic neurotransmission pathways are regulated by dietary iron and provides a molecular basis for the role of iron loading in improved memory.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, United States of America.

ABSTRACT
While nutritional and neurobehavioral problems are associated with both iron deficiency during growth and overload in the elderly, the effect of iron loading in growing ages on neurobehavioral performance has not been fully explored. To characterize the role of dietary iron loading in memory function in the young, weanling rats were fed iron-loading diet (10,000 mg iron/kg diet) or iron-adequate control diet (50 mg/kg) for one month, during which a battery of behavioral tests were conducted. Iron-loaded rats displayed elevated non-heme iron levels in serum and liver, indicating a condition of systemic iron overload. In the brain, non-heme iron was elevated in the prefrontal cortex of iron-loaded rats compared with controls, whereas there was no difference in iron content in other brain regions between the two diet groups. While iron loading did not alter motor coordination or anxiety-like behavior, iron-loaded rats exhibited a better recognition memory, as represented by an increased novel object recognition index (22% increase from the reference value) than control rats (12% increase; P=0.047). Western blot analysis showed an up-regulation of dopamine receptor 1 in the prefrontal cortex from iron-loaded rats (142% increase; P=0.002). Furthermore, levels of glutamate receptors (both NMDA and AMPA) and nicotinic acetylcholine receptor (nAChR) were significantly elevated in the prefrontal cortex of iron-loaded rats (62% increase in NR1; 70% increase in Glu1A; 115% increase in nAChR). Dietary iron loading also increased the expression of NMDA receptors and nAChR in the hippocampus. These results support the idea that iron is essential for learning and memory and further reveal that iron supplementation during developmental and rapidly growing periods of life improves memory performance. Our investigation also demonstrates that both cholinergic and glutamatergic neurotransmission pathways are regulated by dietary iron and provides a molecular basis for the role of iron loading in improved memory.

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Effect of dietary iron loading on the expression of glutamate AMPA receptors in young rat brain.Prefrontal cortex (A) and hippocampus (B) were collected from rats fed iron-loading or control diet and homogenized for western blot analysis to determine the expression levels of subunits of non-NMDA ionotropic glutamate (AMPA) receptor: Glu1A and Glu2A. Relative intensities of protein bands normalized to actin were determined using Image Lab. Empty and closed bars represent control (Con) and iron-loaded (IL) rats, respectively. Data were presented as means ± SEM (n = 4 per group) and were analyzed using two-sample t-test. * P < 0.05.
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pone.0120609.g006: Effect of dietary iron loading on the expression of glutamate AMPA receptors in young rat brain.Prefrontal cortex (A) and hippocampus (B) were collected from rats fed iron-loading or control diet and homogenized for western blot analysis to determine the expression levels of subunits of non-NMDA ionotropic glutamate (AMPA) receptor: Glu1A and Glu2A. Relative intensities of protein bands normalized to actin were determined using Image Lab. Empty and closed bars represent control (Con) and iron-loaded (IL) rats, respectively. Data were presented as means ± SEM (n = 4 per group) and were analyzed using two-sample t-test. * P < 0.05.

Mentions: Since glutamate and acetylcholine signaling is closely associated with memory performance, we examined if increased recognition memory in iron-loaded rats was due to improved glutamatergic and/or cholinergic responses in the PFC and HPC, two well-defined brain regions for memory function. The NMDA glutamate receptor NR1 subunits were up-regulated in the PFC of iron-loaded rats (62% increase; P = 0.009) with both NR2A and 2B unchanged (Fig. 5A), although NR2B levels trended higher (54% increase; P = 0.070). In the HPC from iron-loaded rats, the levels of NR1 and NR2A subunits were not altered (Fig. 5B), but NR2B levels were significantly higher in iron-loaded rats (144% increase; P = 0.035) compared with controls. Furthermore, the expression levels of AMPA glutamate receptors were differentially regulated in the PFC and HPC (Fig. 6); both Glu1A (70% increase; P = 0.042) and Glu2A (59% increase; P = 0.033) receptors were significantly up-regulated in the PFC of rats with high iron compared with controls, whereas the levels of these receptors were similar in the HPC between the two diet groups. In addition, iron-loaded rats showed a significant up-regulation of nAChR protein levels in the PFC compared with controls (115% increase; P = 0.033; Fig. 7A). Finally, the hippocampal nAChR levels were also significantly elevated in iron-loaded rats (44% increase; P = 0.011; Fig. 7B) compared with controls.


Effect of dietary iron loading on recognition memory in growing rats.

Han M, Kim J - PLoS ONE (2015)

Effect of dietary iron loading on the expression of glutamate AMPA receptors in young rat brain.Prefrontal cortex (A) and hippocampus (B) were collected from rats fed iron-loading or control diet and homogenized for western blot analysis to determine the expression levels of subunits of non-NMDA ionotropic glutamate (AMPA) receptor: Glu1A and Glu2A. Relative intensities of protein bands normalized to actin were determined using Image Lab. Empty and closed bars represent control (Con) and iron-loaded (IL) rats, respectively. Data were presented as means ± SEM (n = 4 per group) and were analyzed using two-sample t-test. * P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4352024&req=5

pone.0120609.g006: Effect of dietary iron loading on the expression of glutamate AMPA receptors in young rat brain.Prefrontal cortex (A) and hippocampus (B) were collected from rats fed iron-loading or control diet and homogenized for western blot analysis to determine the expression levels of subunits of non-NMDA ionotropic glutamate (AMPA) receptor: Glu1A and Glu2A. Relative intensities of protein bands normalized to actin were determined using Image Lab. Empty and closed bars represent control (Con) and iron-loaded (IL) rats, respectively. Data were presented as means ± SEM (n = 4 per group) and were analyzed using two-sample t-test. * P < 0.05.
Mentions: Since glutamate and acetylcholine signaling is closely associated with memory performance, we examined if increased recognition memory in iron-loaded rats was due to improved glutamatergic and/or cholinergic responses in the PFC and HPC, two well-defined brain regions for memory function. The NMDA glutamate receptor NR1 subunits were up-regulated in the PFC of iron-loaded rats (62% increase; P = 0.009) with both NR2A and 2B unchanged (Fig. 5A), although NR2B levels trended higher (54% increase; P = 0.070). In the HPC from iron-loaded rats, the levels of NR1 and NR2A subunits were not altered (Fig. 5B), but NR2B levels were significantly higher in iron-loaded rats (144% increase; P = 0.035) compared with controls. Furthermore, the expression levels of AMPA glutamate receptors were differentially regulated in the PFC and HPC (Fig. 6); both Glu1A (70% increase; P = 0.042) and Glu2A (59% increase; P = 0.033) receptors were significantly up-regulated in the PFC of rats with high iron compared with controls, whereas the levels of these receptors were similar in the HPC between the two diet groups. In addition, iron-loaded rats showed a significant up-regulation of nAChR protein levels in the PFC compared with controls (115% increase; P = 0.033; Fig. 7A). Finally, the hippocampal nAChR levels were also significantly elevated in iron-loaded rats (44% increase; P = 0.011; Fig. 7B) compared with controls.

Bottom Line: While nutritional and neurobehavioral problems are associated with both iron deficiency during growth and overload in the elderly, the effect of iron loading in growing ages on neurobehavioral performance has not been fully explored.These results support the idea that iron is essential for learning and memory and further reveal that iron supplementation during developmental and rapidly growing periods of life improves memory performance.Our investigation also demonstrates that both cholinergic and glutamatergic neurotransmission pathways are regulated by dietary iron and provides a molecular basis for the role of iron loading in improved memory.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, United States of America.

ABSTRACT
While nutritional and neurobehavioral problems are associated with both iron deficiency during growth and overload in the elderly, the effect of iron loading in growing ages on neurobehavioral performance has not been fully explored. To characterize the role of dietary iron loading in memory function in the young, weanling rats were fed iron-loading diet (10,000 mg iron/kg diet) or iron-adequate control diet (50 mg/kg) for one month, during which a battery of behavioral tests were conducted. Iron-loaded rats displayed elevated non-heme iron levels in serum and liver, indicating a condition of systemic iron overload. In the brain, non-heme iron was elevated in the prefrontal cortex of iron-loaded rats compared with controls, whereas there was no difference in iron content in other brain regions between the two diet groups. While iron loading did not alter motor coordination or anxiety-like behavior, iron-loaded rats exhibited a better recognition memory, as represented by an increased novel object recognition index (22% increase from the reference value) than control rats (12% increase; P=0.047). Western blot analysis showed an up-regulation of dopamine receptor 1 in the prefrontal cortex from iron-loaded rats (142% increase; P=0.002). Furthermore, levels of glutamate receptors (both NMDA and AMPA) and nicotinic acetylcholine receptor (nAChR) were significantly elevated in the prefrontal cortex of iron-loaded rats (62% increase in NR1; 70% increase in Glu1A; 115% increase in nAChR). Dietary iron loading also increased the expression of NMDA receptors and nAChR in the hippocampus. These results support the idea that iron is essential for learning and memory and further reveal that iron supplementation during developmental and rapidly growing periods of life improves memory performance. Our investigation also demonstrates that both cholinergic and glutamatergic neurotransmission pathways are regulated by dietary iron and provides a molecular basis for the role of iron loading in improved memory.

Show MeSH
Related in: MedlinePlus