Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuronal transferrin receptor protein expression is highly upregulated widely in CNS following iron deficiency. Using the medial habenular nucleus as a model of neuronal transferrin receptor mRNA expression, the present study examined 17-day-old rats subjected to variations in dietary iron. Changing the iron availability resulted in alterations in plasma and cerebrospinal fluid (CSF) levels of transferrin and iron. The iron-binding capacity of transferrin in CSF was exceeded in normal and iron-overloaded rats. In spite of a lowering of the concentration of brain iron by approximately 22% in iron-deficient rats, neuronal transferrin receptor mRNA was not affected when measured by quantitative densitometry. Brain iron and neuronal transferrin receptor mRNA expression was unaltered in iron overloaded rats. The absence of a rise in transferrin receptor mRNA during iron deficiency suggests that neuronal transferrin receptor mRNA expression is regulated by another mechanism than the post-transcriptional regulation mechanism, which has been attributed to cells of non-neural tissue.
 ...
PMID:Iron-independent neuronal expression of transferrin receptor mRNA in the rat. 1052 82

Calcium and iron play dual roles in neuronal function: they are both essential but when present in excess they cause neuronal damage and may even induce neuronal death. Calcium signals are required for synaptic plasticity, a neuronal process that entails gene expression and which is presumably the cellular counterpart of cognitive brain functions such as learning and memory. Neuronal activity generates cytoplasmic and nuclear calcium signals that in turn stimulate pathways that promote the transcription of genes known to participate in synaptic plasticity. In addition, evidence discussed in this article shows that iron deficiency causes learning and memory impairments that persist following iron repletion, indicating that iron is necessary for normal development of cognitive functions. Recent results from our group indicate that iron is required for long-term potentiation in hippocampal CA1 neurons and that iron stimulates ryanodine receptor-mediated calcium release through ROS produced via the Fenton reaction leading to stimulation of the ERK signaling pathway. These combined results support a coordinated action between iron and calcium in synaptic plasticity and raise the possibility that elevated iron levels may contribute to neuronal degeneration through excessive intracellular calcium increase caused by iron-induced oxidative stress.
 ...
PMID:Calcium, iron and neuronal function. 1750 66

Iron deficiency (ID) is the most prevalent micronutrient deficiency in the world and it affects neurobehavioral outcome. It is unclear whether the effect of dietary ID on the brain is due to the lack of neuronal iron or from other processes occurring in conjunction with ID (e.g. hypoxia due to anemia). We delineated the role of murine Slc11a2 [divalent metal ion transporter-1 (DMT-1)] in hippocampal neuronal iron uptake during development and memory formation. Camk2a gene promoter-driven cre recombinase (Cre) transgene (Camk2a-Cre) mice were mated with Slc11a2 flox/flox mice to obtain nonanemic Slc11a2(hipp/hipp) (double mutant, hippocampal neuron-specific knockout of Slc11a2(hipp/hipp)) mice, the first conditionally targeted model of iron uptake in the brain. Slc11a2(hipp/hipp) mice had lower hippocampal iron content; altered developmental expression of genes involved in iron homeostasis, energy metabolism, and dendrite morphogenesis; reductions in markers for energy metabolism and glutamatergic neurotransmission on magnetic resonance spectroscopy; and altered pyramidal neuron dendrite morphology in area 1 of Ammon's Horn in the hippocampus. Slc11a2(hipp/hipp) mice did not reach the criterion on a difficult spatial navigation test but were able to learn a spatial navigation task on an easier version of the Morris water maze (MWM). Learning of the visual cued task did not differ between the Slc11a2(WT/WT) and Slc11a2(hipp/hipp) mice. Slc11a2(WT/WT) mice had upregulation of genes involved in iron uptake and metabolism in response to MWM training, and Slc11a2(hipp/hipp) mice had differential expression of these genes compared with Slc11a2(WT/WT) mice. Neuronal iron uptake by DMT-1 is essential for normal hippocampal neuronal development and Slc11a2 expression is induced by spatial memory training. Deletion of Slc11a2 disrupts hippocampal neuronal development and spatial memory behavior.
 ...
PMID:Iron is essential for neuron development and memory function in mouse hippocampus. 1921 31

Neuronal iron homeostasis disruption and oxidative stress are closely related to the pathogenesis of Parkinson's disease (PD). Adult iron-regulatory protein 2 knockout (Ireb2(-/-)) mice develop iron accumulation in white matter tracts and nuclei in different brain area and display severe neurodegeneration in Purkinje cells of the cerebrum. Mitochondrial ferritin (MtFt), a newly discovered ferritin, specifically expresses in high energy-consuming cells, including neurons of brain and spinal cord. Interestingly, the decreased expression of MtFt in cerebrum, but not in striatum, matches the differential neurodegeneration pattern in these Ireb2(-/-) mice. To explore its effect on neurodegeneration, the effects of MtFt expression on 6-hydrodopamine (6-OHDA)-induced neuronal damage was examined. The overexpression of MtFt led to a cytosolic iron deficiency in the neuronal cells and significantly prevented the alteration of iron redistribution induced by 6-OHDA. Importantly, MtFt strongly inhibited mitochondrial damage, decreased production of the reactive oxygen species and lipid peroxidation, and dramatically rescued apoptosis by regulating Bcl-2, Bax and caspase-3 pathways. In conclusion, this study demonstrates that MtFt plays an important role in preventing neuronal damage in an 6-OHDA-induced parkinsonian phenotype by maintaining iron homeostasis. Regulation of MtFt expression in neuronal cells may provide a new neuroprotective strategy for PD.
 ...
PMID:Neuroprotective mechanism of mitochondrial ferritin on 6-hydroxydopamine-induced dopaminergic cell damage: implication for neuroprotection in Parkinson's disease. 2012 42