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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 systemic iron status in growing rats.Weanling rats were fed control (50 mg iron/kg diet) or iron-loading diet (10,000 mg iron as carbonyl iron per kg diet) for one month and euthanized to collect blood, serum and liver. For systemic iron status, hematocrit (A) and the levels of serum iron (B) and liver non-heme iron (C) were determined. Empty and closed bars represent control (Con) and iron-loaded (IL) rats, respectively. Data were presented as means ± SEM (n = 6 per group) and were analyzed using two-sample t-test. * P < 0.05.
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pone.0120609.g001: Effect of dietary iron loading on systemic iron status in growing rats.Weanling rats were fed control (50 mg iron/kg diet) or iron-loading diet (10,000 mg iron as carbonyl iron per kg diet) for one month and euthanized to collect blood, serum and liver. For systemic iron status, hematocrit (A) and the levels of serum iron (B) and liver non-heme iron (C) were determined. Empty and closed bars represent control (Con) and iron-loaded (IL) rats, respectively. Data were presented as means ± SEM (n = 6 per group) and were analyzed using two-sample t-test. * P < 0.05.

Mentions: Weanling male rats were fed control or iron loading (10,000 mg iron/kg) diet over a month. Iron loading diet decreased body weight (274 ± 8 g; n = 12) compared with controls (318 ± 10 g; n = 16; P = 0.004), although total food intake per body weight was not different (data not shown). Decreased body weight upon iron loading was previously reported in rats fed 3,500 and 20,000 ppm iron [39]. While hematocrit values were unchanged upon iron loading (Fig. 1A), iron-loaded rats displayed significantly elevated levels of iron in serum (Fig. 1B) and liver (Fig. 1C), indicating a condition of systemic iron loading due to increased dietary iron. To examine if dietary iron loading in growing rats also increases iron stores in the brain, the left brain hemisphere from rats fed either control or iron loading diet was microdissected for iron analysis. Non-heme iron levels in the PFC were significantly elevated in iron-loaded rats compared with controls (P = 0.018; n = 5–6/group), while those in other regions (i.e., striatum, hippocampus and cerebellum) did not significantly differ between the two groups (Table 1).


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

Han M, Kim J - PLoS ONE (2015)

Effect of dietary iron loading on systemic iron status in growing rats.Weanling rats were fed control (50 mg iron/kg diet) or iron-loading diet (10,000 mg iron as carbonyl iron per kg diet) for one month and euthanized to collect blood, serum and liver. For systemic iron status, hematocrit (A) and the levels of serum iron (B) and liver non-heme iron (C) were determined. Empty and closed bars represent control (Con) and iron-loaded (IL) rats, respectively. Data were presented as means ± SEM (n = 6 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.g001: Effect of dietary iron loading on systemic iron status in growing rats.Weanling rats were fed control (50 mg iron/kg diet) or iron-loading diet (10,000 mg iron as carbonyl iron per kg diet) for one month and euthanized to collect blood, serum and liver. For systemic iron status, hematocrit (A) and the levels of serum iron (B) and liver non-heme iron (C) were determined. Empty and closed bars represent control (Con) and iron-loaded (IL) rats, respectively. Data were presented as means ± SEM (n = 6 per group) and were analyzed using two-sample t-test. * P < 0.05.
Mentions: Weanling male rats were fed control or iron loading (10,000 mg iron/kg) diet over a month. Iron loading diet decreased body weight (274 ± 8 g; n = 12) compared with controls (318 ± 10 g; n = 16; P = 0.004), although total food intake per body weight was not different (data not shown). Decreased body weight upon iron loading was previously reported in rats fed 3,500 and 20,000 ppm iron [39]. While hematocrit values were unchanged upon iron loading (Fig. 1A), iron-loaded rats displayed significantly elevated levels of iron in serum (Fig. 1B) and liver (Fig. 1C), indicating a condition of systemic iron loading due to increased dietary iron. To examine if dietary iron loading in growing rats also increases iron stores in the brain, the left brain hemisphere from rats fed either control or iron loading diet was microdissected for iron analysis. Non-heme iron levels in the PFC were significantly elevated in iron-loaded rats compared with controls (P = 0.018; n = 5–6/group), while those in other regions (i.e., striatum, hippocampus and cerebellum) did not significantly differ between the two groups (Table 1).

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