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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 dopamine transporters and dopamine receptors in young rat brain.Prefrontal cortex (A and C) and hippocampus (B and D) were collected from rats fed iron-loading or control diet and homogenized for western blot analysis to determine the expression levels of dopamine transporter (A and B) or dopamine D1 receptor (C and D). Relative intensities of protein bands normalized to actin were determined using Image Lab (version 4.1). 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.g004: Effect of dietary iron loading on the expression of dopamine transporters and dopamine receptors in young rat brain.Prefrontal cortex (A and C) and hippocampus (B and D) were collected from rats fed iron-loading or control diet and homogenized for western blot analysis to determine the expression levels of dopamine transporter (A and B) or dopamine D1 receptor (C and D). Relative intensities of protein bands normalized to actin were determined using Image Lab (version 4.1). 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 dopamine plays an important role in learning capacity and since D1R has been shown to modulate working memory-related neural activity [53], we quantified DAT and D1R in the PFC and HPC. There was no significant difference in DAT levels in either PFC or HPC between two groups of rats (Fig. 4, A and B). In contrast, iron-loaded rats up-regulated D1R protein levels in the PFC compared with controls (142% increase; P = 0.002; Fig. 4C). The expression levels of D1R in the HPC from iron-loaded rats trended higher (P = 0.089; Fig. 4D), although statistically insignificant.


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 dopamine transporters and dopamine receptors in young rat brain.Prefrontal cortex (A and C) and hippocampus (B and D) were collected from rats fed iron-loading or control diet and homogenized for western blot analysis to determine the expression levels of dopamine transporter (A and B) or dopamine D1 receptor (C and D). Relative intensities of protein bands normalized to actin were determined using Image Lab (version 4.1). 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

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

pone.0120609.g004: Effect of dietary iron loading on the expression of dopamine transporters and dopamine receptors in young rat brain.Prefrontal cortex (A and C) and hippocampus (B and D) were collected from rats fed iron-loading or control diet and homogenized for western blot analysis to determine the expression levels of dopamine transporter (A and B) or dopamine D1 receptor (C and D). Relative intensities of protein bands normalized to actin were determined using Image Lab (version 4.1). 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 dopamine plays an important role in learning capacity and since D1R has been shown to modulate working memory-related neural activity [53], we quantified DAT and D1R in the PFC and HPC. There was no significant difference in DAT levels in either PFC or HPC between two groups of rats (Fig. 4, A and B). In contrast, iron-loaded rats up-regulated D1R protein levels in the PFC compared with controls (142% increase; P = 0.002; Fig. 4C). The expression levels of D1R in the HPC from iron-loaded rats trended higher (P = 0.089; Fig. 4D), although statistically insignificant.

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