Hippocampus specific iron deficiency alters competition and cooperation between developing memory systems

Carlson, Edward C.; Fretham, Stephanie J. B.; Unger, Erica L.; O’Connor, Michael B.; Petryk, Anna; Schallert, Timothy; Rao, Raghavendra; Tkáč, Ivan; Georgieff, Michael

doi:10.1007/s11689-010-9049-0

Cited by 45 publications

(59 citation statements)

References 70 publications

(128 reference statements)

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“…Disruption of this process by nutritional deficiency during foetal, childhood, or adolescent development has been linked to behavioural and neuronal deficits707172. In the developing brain, iron is closely related to neuro-inflammation, potentially caused by stress and nutrition73.…”

Section: Discussionmentioning

confidence: 99%

Insula and somatosensory cortical myelination and iron markers underlie individual differences in empathy

Allen

Frank

Glen

et al. 2017

Sci Rep

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Empathy is a key component of our ability to engage and interact with others. In recent years, the neural mechanisms underlying affective and cognitive empathy have garnered intense interest. This work demonstrates that empathy for others depends upon a distributed network of regions such as the insula, parietal cortex, and somatosensory areas, which are also activated when we ourselves experience an empathized-with emotion (e.g., pain). Individuals vary markedly in their ability to empathize with others, which predicts the tendency to help others and relates to individual differences in the neuroanatomy of these areas. Here, we use a newly developed, high-resolution (800 μm isotropic), quantitative MRI technique to better elucidate the neuroanatomical underpinnings of individual differences in empathy. Our findings extend previous studies of the neuroanatomical correlates of cognitive and affective empathy. In particular, individual differences in cognitive empathy were associated with markers of myeloarchitectural integrity of the insular cortex, while affective empathy was predicted by a marker of iron content in second somatosensory cortex. These results indicate potential novel biomarkers of trait empathy, suggesting that microstructural features of an empathy and body-related network are crucial for understanding the mental and emotional states of others.

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Section: Discussionmentioning

confidence: 99%

Insula and somatosensory cortical myelination and iron markers underlie individual differences in empathy

Allen

Frank

Glen

et al. 2017

Sci Rep

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“…Previous research has shown that the hippocampus is essential for the development of many behaviors (including learning and memory) and that low iron can negatively affect behavioral development (49). Iron deficiency can disrupt the dopamine pathway to alter certain forms of learning (50,51).…”

Section: Discussionmentioning

confidence: 99%

Early Life Iron Deficiency Impairs Spatial Cognition in Neonatal Piglets ,2

Rytych

Elmore

Burton

et al. 2012

The Journal of Nutrition

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Iron deficiency is common throughout the world and has been linked to cognitive impairments. Using neonatal piglets to model human infants, we assessed the impact of iron deficiency on spatial learning and memory. Artificially reared piglets were fed 1 of 3 liquid diets with varying concentrations of iron: control (CON), mildly deficient (MID), or severely deficient (SID; 100, 25.0, or 10.0 mg iron/kg milk solids, respectively) for 4 wk. Relative to CON, SID and MID piglets had reduced hemoglobin (P < 0.05) as well as magenta skin color (P < 0.001), which correlated with hematocrit (R(2) = 0.76; P < 0.001). SID and MID hemoglobin differed at wk 3 and 4 (P < 0.05). In a hippocampal-dependent, spatial, T-maze task, SID piglets were unable to acquire the task (post hoc contrast: first vs. last day of acquisition), while MID piglets demonstrated deficits in reversal learning (P = 0.032). Iron concentrations in the liver (P < 0.001), serum (P = 0.003), and hippocampus (P = 0.004), but not prefrontal cortex, were lower in MID and SID compared with CON piglets. The level of the transferrin receptor mRNA (TFR) was greater in the prefrontal cortex of CON piglets than in MID and SID piglets (P = 0.001) but not the hippocampus. Gene expression of several neurotrophic factors and proinflammatory cytokines, as well as whole-brain and hippocampal volume, were not affected by dietary treatment. In conclusion, neonatal iron deficiency leads to cognitive impairment, which may be due in part to a reduced iron concentration in the hippocampus.

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“…Of the significant genes in this pathway, Slc11a2 deficiency has been associated with hippocampal iron levels and related cognitive and neurodevelopmental traits in rodents (Carlson et al, 2010;Pisansky et al, 2013). VAMP7 is suggested to play a role in neural transmission (Bal et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Exome Sequencing to Detect Rare Variants Associated With General Cognitive Ability: A Pilot Study

et al. 2015

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Variation in human cognitive ability is of consequence to a large number of health and social outcomes and is substantially heritable. Genetic linkage, genome-wide association, and copy number variant studies have investigated the contribution of genetic variation to individual differences in normal cognitive ability, but little research has considered the role of rare genetic variants. Exome sequencing studies have already met with success in discovering novel trait-gene associations for other complex traits. Here, we use exome sequencing to investigate the effects of rare variants on general cognitive ability. Unrelated Scottish individuals were selected for high scores on a general component of intelligence (g). The frequency of rare genetic variants (in n = 146) was compared with those from Scottish controls (total n = 486) who scored in the lower to middle range of the g distribution or on a proxy measure of g. Biological pathway analysis highlighted enrichment of the mitochondrial inner membrane component and apical part of cell gene ontology terms. Global burden analysis showed a greater total number of rare variants carried by high g cases versus controls, which is inconsistent with a mutation load hypothesis whereby mutations negatively affect g. The general finding of greater non-synonymous (vs. synonymous) variant effects is in line with evolutionary hypotheses for g. Given that this first sequencing study of high g was small, promising results were found, suggesting that the study of rare variants in larger samples would be worthwhile.

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Hippocampus specific iron deficiency alters competition and cooperation between developing memory systems

Cited by 45 publications

References 70 publications

Insula and somatosensory cortical myelination and iron markers underlie individual differences in empathy

Insula and somatosensory cortical myelination and iron markers underlie individual differences in empathy

Early Life Iron Deficiency Impairs Spatial Cognition in Neonatal Piglets ,2

Exome Sequencing to Detect Rare Variants Associated With General Cognitive Ability: A Pilot Study

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