Effect of manipulation of iron storage, transport, or availability on myelin composition and brain iron content in three different animal models

Biological Chemistry Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
Journal of Neuroscience Research (Impact Factor: 2.59). 09/2004; 77(5):681-9. DOI: 10.1002/jnr.20207
Source: PubMed


Several observations suggest that iron is an essential factor in myelination and oligodendrocyte biology. However, the specific role of iron in these processes remains to be elucidated. This role could be as an essential cofactor in metabolic processes or as a transcriptional or translational regulator. In this study, we used animals models each with a unique defect in iron availability, storage, or transfer to test the hypothesis that disruptions in these mechanisms affect myelinogenesis and myelin composition. Disruption of iron availability either by limiting dietary iron or by altering iron storage capacity resulted in a decrease in myelin proteins and lipids but not the iron content of myelin. Among the integral myelin proteins, proteolipid protein was most consistently affected, suggesting that limiting iron to oligodendrocytes results not only in hypomyelination but also in a decrease in myelin compaction. Mice deficient in transferrin must receive transferrin injections beginning at birth to remain viable, and these mice had increases in all of the myelin components and in the iron content of the myelin. This finding indicates that the loss of endogenous iron mobility in oligodendrocytes could be overcome by application of exogenous transferrin. Overall, the results of this study demonstrate how myelin composition can be affected by loss of iron homeostasis and reveal specific chronic changes in myelin composition that may affect behavior and attempts to rescue myelin deficits.

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    • "e, deri ve mukozalarda önemli değişiklikler ortaya çıkmaktadır (Ağaoğlu 2010). Demirin, pek çok biyolojik işlevi yanında, miyelinizasyon, oligodendrositlerin gelişimi, nörotransmitter sentezi gibi nörobiyolojik süreçler üzerine olan etkisi oldukça önemlidir (Lozoff ve ark. 1987, Beard ve ark. 1993, Connor ve Menzies 1996, Roncagliolo ve ark. 1998, Ortiz ve ark. 2004). Demir eksikliğinin, santral sinir sistemi üzerine olan etkileri; halsizlik, aktivite azalması, irritabilite, iletişim bozuklukları, okul başarısında düşme, mental-motor gelişim testlerinde performans düşüklüğü, kognitif performansta azalma, papil ödem olarak sıralanabilir (Ekici 2012). Demir eksikliğinin, psikomotor gelişim ve öğrenme"
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    • "Effects on myelination Iron is needed for myelination Features of AD include white matter hyperintensity, axonal, neurite and synaptic changes Impaired neurotransmission Ortiz et al., 2004; Bartzokis et al., 2007; Baeten et al., 2010; Romero et al., 2010; Paling et al., 2012 staining is not covered here, but has been recently reviewed with a focus on neurobiology (Que et al., 2008). "
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    Frontiers in Aging Neuroscience 07/2014; 6:138. DOI:10.3389/fnagi.2014.00138 · 4.00 Impact Factor
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    • "With iron in being integral part of numerous cellular metabolic activities [1] [2], its homeostasis is controlled by a large group of iron-regulatory proteins, but it excess in the body becomes potentially toxic to the cell because mammals lack a regulatory pathway for its excretion [3]. Erythrocytes besides spleen and liver contain the majority of body iron as a component of hemoglobin and circulate throughout the body for vital redox biological processes. "
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