Postnatal nutritional iron deficiency impairs dopaminergic-mediated synaptic plasticity in the CA1 area of the hippocampus

Breton, Ashley B.; Fox, Julia A.; Brownson, Mary; McEchron, Matthew D.

doi:10.1179/1476830514y.0000000121

Cited by 8 publications

(7 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…What is more, nose pokes and rates of habituation were related to prefrontal cortical iron levels, whereas spontaneous activities, which had higher correlation with iron concentrations and the density of dopamine receptors in the ventral midbrain (Han and Kim, 2015). Another study also showed that iron levels in the brain are one of critical factors for anxiety-like behaviors (Breton et al., 2015). Thus, it is clear that ID can be detrimental to brain development and can increase the risk of poor neurodevelopment both in premature newborns and in neonatal animal models.…”

Section: Impact Of Iron Imbalance On Brain Development In Preterm Infmentioning

confidence: 99%

Iron Metabolism and Brain Development in Premature Infants

Wang

et al. 2019

Front. Physiol.

View full text Add to dashboard Cite

Iron is important for a remarkable array of essential functions during brain development, and it needs to be provided in adequate amounts, especially to preterm infants. In this review article, we provide an overview of iron metabolism and homeostasis at the cellular level, as well as its regulation at the mRNA translation level, and we emphasize the importance of iron for brain development in fetal and early life in preterm infants. We also review the risk factors for disrupted iron metabolism that lead to high risk of developing iron deficiency and subsequent adverse effects on neurodevelopment in preterm infants. At the other extreme, iron overload, which is usually caused by excess iron supplementation in iron-replete preterm infants, might negatively impact brain development or even induce brain injury. Maintaining the balance of iron during the fetal and neonatal periods is important, and thus iron status should be monitored routinely and evaluated thoroughly during the neonatal period or before discharge of preterm infants so that iron supplementation can be individualized.

show abstract

Section: Impact Of Iron Imbalance On Brain Development In Preterm Infmentioning

confidence: 99%

Iron Metabolism and Brain Development in Premature Infants

Wang

et al. 2019

Front. Physiol.

View full text Add to dashboard Cite

show abstract

“…Iron is an essential co-factor for enzymes involved in a variety of normal neuronal functions (Altamura and Muckenthaler 2009). Insufficient iron impairs neuronal development (Greminger et al 2014; Matak et al 2016; Breton et al 2015), while brain iron accumulation is associated with aging and neurodegeneration (Ghadery et al 2015; Dexter et al 1991). Such neurological disorders include Alzheimer’s and Parkinson’s diseases (Smith et al 1997; Dexter et al 1987).…”

Section: Introductionmentioning

confidence: 99%

The Ferroxidase Hephaestin But Not Amyloid Precursor Protein is Required for Ferroportin-Supported Iron Efflux in Primary Hippocampal Neurons

Steimle

Bailey

et al. 2017

Cell Mol Neurobiol

View full text Add to dashboard Cite

Iron efflux in mammalian cells is mediated by the ferrous iron exporter ferroportin (Fpn); Fpn plasma membrane localization and function are supported by a multicopper ferroxidase and/or the soluble amyloid precursor protein (sAPP). Fpn and APP are ubiquitously expressed in all cell types in the central nervous system including neurons. In contrast, neuronal ferroxidase(s) expression has not been well characterized. Using primary cultures of hippocampal neurons, we examined the molecular mechanism of neuronal Fe efflux in detail. Developmental increases of Fpn, APP, and the ferroxidase hephaestin (Hp) were observed in hippocampal neurons. Iron efflux in these neurons depended on the level of Fpn localized at the cell surface; as noted, Fpn stability is supported by ferroxidase activity, an enzymatic activity that is required for Fe efflux. Iron accumulation increases and iron efflux decreases in Hp knockout neurons. In contrast, suppression of endogenous APP by RNAi knockdown does not affect surface Fpn stability or Fe efflux. These data support the model that the neuronal ferroxidase Hp plays a unique role in support of Fpn-mediated Fe efflux in primary hippocampal neurons. Our data also demonstrate that Hp ferroxidase activity relies on copper bioavailability, which suggests neuronal iron homeostasis will be modulated by cellular copper status.

show abstract

“…Here we observed iron homeostasis genes are differentially regulated by PAE in several regions of the brain, perhaps modulating a coordinated activation of different regions involved in cognition, in special between PFC and hippocampus, where we found the more consistent observations described above. Moreover an iron deficient diet can affect hippocampal plasticity by impairing dopaminergic-mediated synaptic plasticity (Breton et al, 2015), disruption of synaptic maturation (Jorgenson et al, 2005), or by abnormality of the CA1 apical dendrite structure (Fretham et al, 2011; Muñoz and Humeres, 2012).…”

Section: Discussionmentioning

confidence: 99%

Prenatal Ethanol Exposure Misregulates Genes Involved in Iron Homeostasis Promoting a Maladaptation of Iron Dependent Hippocampal Synaptic Transmission and Plasticity

et al. 2019

View full text Add to dashboard Cite

Prenatal ethanol exposure (PAE) induces behavioral maladptations in offspring, including a deficit in memory formation which is part of the umbrella sign of fetal alcohol spectrum disorder. Clinical and preclinical studies have shown that iron depletion exacerbates cognitive problems in offspring exposed to ethanol in utero and that PAE promotes dysregulation in brain iron homeostasis. However, the mechanisms underlying brain iron dysregulation and neuronal activity defects in adolescent offspring of PAE are unclear and poorly understand. Here, we used a PAE rat model to analyze messenger RNA (mRNA) and protein expression of iron homeostasis genes such as transferrin receptor (TfR), divalent metal transporter (DMT1), ferroportin (FPN1), and ferritin (FT) in brain areas associated with memory formation such as the prefrontal cortex (PFC), ventral tegmental area, and hippocampus. Interestingly, we found that 21 day old PAE rats have higher mRNA expression of DMT1 in the PFC, and TfR in the hippocampus, compared to control animals. In contrast FPN has lower mRNA expression in the PFC, and FT and FPN1 have lower expression in the hippocampus. In agreement with these results, we found a 1.5–2 fold increase of TfR and DMT1 protein levels both in the hippocampus and the PFC. Additionally, using an electrophysiological approach, we found that in hippocampal slices from PAE rats, iron treatment decreased long-term potentiation (LTP), but not AMPAR basal transmission (AMPAR fEPSP). In contrast, in control slices Fe-NTA did not affect LTP but decreased significantly the AMPAR fEPSP. Meanwhile, iron chelation with deferiprone decreased AMPAR transmission in PAE and control slices and decreased LTP only in controls slices. These results suggest that PAE affects iron homeostasis of specific brain areas—PFC and hippocampus—which could be involved in maladaptive cognition observed in this animal model.

show abstract

Postnatal nutritional iron deficiency impairs dopaminergic-mediated synaptic plasticity in the CA1 area of the hippocampus

Abstract: The present study demonstrates that postnatal ID produces long-lasting impairments in dopaminergic-dependent synaptic plasticity in the hippocampus. These impairments may play a role in the learning and memory deficits known to result from ID.

Cited by 8 publications

References 20 publications

Iron Metabolism and Brain Development in Premature Infants

Iron Metabolism and Brain Development in Premature Infants

The Ferroxidase Hephaestin But Not Amyloid Precursor Protein is Required for Ferroportin-Supported Iron Efflux in Primary Hippocampal Neurons

Prenatal Ethanol Exposure Misregulates Genes Involved in Iron Homeostasis Promoting a Maladaptation of Iron Dependent Hippocampal Synaptic Transmission and Plasticity

Contact Info

Product

Resources

About