Oligodendrocyte differentiation is increased in transferrin transgenic mice

Sow, A.I.; Lamant, Matthieu; Bonny, Jean‐Marie; Larvaron, Pierre; Piaud, Oriane; Lécureuil, Charlotte; Fontaine, I.; Saleh, María-Carla; Otin, Angel Luis Garcia; Renou, Jean-Pierre; Baron, Bruno; Zakin, Mario M.; Guillou, Florian

doi:10.1002/jnr.20741

Cited by 31 publications

(25 citation statements)

References 61 publications

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“…The Tf can selectively regulate MBP expression at the transcriptional level and increase the differentiation, maturation and myelination of OLs (EspinosaJeffrey et al 2002;Sow et al 2006). Thus, our finding that high expression of Tf in OLs is consistent with previous report.…”

Section: Candidate Genes That May Intrinsically Control Ol-specific Dsupporting

confidence: 92%

Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes

Wang

Zhou

et al. 2011

Tohoku J. Exp. Med.

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Oligodendrocyte precursor cells (OPCs) are bipotential progenitor cells that can differentiate into myelin-forming oligodendrocytes or functionally undetermined type II astrocytes. Transplantation of OPCs is an attractive therapy for demyelinating diseases. However, due to their bipotential differentiation potential, the majority of OPCs differentiate into astrocytes at transplanted sites. It is therefore important to understand the molecular mechanisms that regulate the transition from OPCs to oligodendrocytes or astrocytes. In this study, we isolated OPCs from the spinal cords of rat embryos (16 days old) and induced them to differentiate into oligodendrocytes or type II astrocytes in the absence or presence of 10% fetal bovine serum, respectively. RNAs were extracted from each cell population and hybridized to GeneChip with 28,700 rat genes. Using the criterion of fold change > 4 in the expression level, we identified 83 genes that were up-regulated and 89 genes that were down-regulated in oligodendrocytes, and 92 genes that were up-regulated and 86 that were down-regulated in type II astrocytes compared with OPCs. The up-regulated genes, such as activating transcription factor 3 and myelin basic protein in oligodendrocytes or claudin 11 in type II astrocytes, might contribute to OPC differentiation and represent constitutive components of oligodendrocytes or type II astrocytes. The down-regulated genes in both oligodendrocytes and type II astrocytes, such as transcription factor 19, might be involved in maintaining self-renewal and/or represent the property of OPCs. These results provide new insights into the elucidation of the molecular mechanisms, by which OPCs differentiate to oligodendrocytes or type II astrocytes.

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Section: Candidate Genes That May Intrinsically Control Ol-specific Dsupporting

confidence: 92%

Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes

Wang

Zhou

et al. 2011

Tohoku J. Exp. Med.

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“…However, most of the soluble iron in any biological system is in the ferrous form, and would have to be converted to ferric iron before it would bind to Tf. The elevated production of myelin is consistent with elevated myelination associated with over-expression of Tf by oligodendrocytes (Saleh et al, 2003, Sow et al, 2006.…”

Section: Transferrin: Role In Iron Import and Myelinationsupporting

confidence: 50%

“…The hypermyelinating effect of transferrin overexpression had no effect on mouse locomotion, cognitive and emotional abilities, and electron microscopic analysis showed myelin of normal thickness and compaction (Saleh et al, 2003). Using the same mouse model, Sow et al (2006) showed that OPCs cultured from brains of these mice show accelerated differentiation [expression of O4 and PLP markers (O4 and O1, markers of pro-oligodendrocytes)] as well as increased expression of Sox 10 and Olig1 mRNA and protein. These observations suggest that the overexpression of transferrin in oligodendrocytes in this model stimulates accelerated differentiation (i.e., earlier production of normal myelin), but not necessarily more myelin.…”

Section: Transferrin: Role In Iron Import and Myelinationmentioning

confidence: 93%

Oligodendrocytes and myelination: The role of iron

Todorich

Pasquini

Garcı́a

et al. 2008

Glia

524

409

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Iron is an essential trophic factor that is required for oxygen consumption and ATP production. Thus it plays a key role in vital cell functions. Although the brain has a relatively high rate of oxygen consumption compared to other organs, oligodendrocytes are the principal cells in the CNS that stain for iron under normal conditions. The importance of iron in myelin production has been demonstrated by studies showing that decreased availability of iron in the diet is associated with hypomyelination. The timing of iron delivery to oligodendrocytes during development is also important because hypomyelination and the associated neurological sequelae persist long after the systemic iron deficiency has been corrected. Therefore, identifying the molecular roles of iron in oligodendrocyte development and myelin production, and the mechanisms and timing of iron acquisitions are important prerequisites to developing effective therapies for dysmyelinating disorders. It is the purpose of this review to give a comprehensive overview of the existing literature on role of iron in oligodendrocytes and the mechanisms of iron acquisition and intracellular handling.

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“…Of note, an increase in CSF asialotransferrin to transferrin ratio has been reported in patients with congenital disorders of glycosylation since these disorders have been recognized. 30 There is increasing evidence that transferrin plays a role in oligodendrocyte maturation and homeostasis, [31][32][33][34][35][36][37] in addition to its known role in iron metabolism and oxidative stress. 38 Thus, decreased asialotransferrin to transferrin ratio in the CSF may simply be a manifestation of disturbed protein homeostasis within the CNS as a result of EIF2B mutations, or it may play a role in the pathophysiology of the disorder.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity and specificity of decreased CSF asialotransferrin for eIF2B-related disorder

Vanderver¹,

Hathout²,

Maletkovic³

et al. 2008

Neurology

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Objective-This is a study estimating diagnostic accuracy of CSF asialotransferrin to transferrin ratio measurement in eIF2B related disorders by using clinical evaluation and EIF2B mutation analysis as the reference standard. eIF2B-related disorder is a relatively common leukodystrophy with broad phenotypic variation that is caused by mutations in any of the five EIF2B genes. There is a need for a simple and clinically valid screening tool for physicians evaluating patients with an unclassified leukodystrophy.Methods-CSF two-dimensional gel (2DG) electrophoresis analyses to measure asialotransferrin to transferrin ratios were performed in 60 subjects including 6 patients with documented EIF2B gene mutations, patients with other types of leukodystrophy, and patients with no leukodystrophy.Results-All six patients with mutation proven eIF2B-related disease showed low to nearly undetectable amounts of asialotransferrin in their CSF when compared to 54 unaffected controls by CSF 2DG analyses in this study. eIF2B-like patients, with clinically similar presentations but no mutations in EIF2B1-5, were distinguished from patients with mutations in EIF2B1-5 by this biomarker. Patients with mutations in EIF2B1-5 had asialotransferrin/transferrin ratio levels significantly different from the group as a whole (p < 0.001). Using 8% asialotransferrin/ transferrin ratio as a cutoff, this biomarker has a 100% sensitivity (95% CI = 52-100%) and 94% specificity (95% CI = 84-99%).Conclusion-Decreased asialotransferrin/transferrin ratio in the CSF of patients with eIF2B-related disorder is highly sensitive and specific. This rapid (<48 hours) and inexpensive diagnostic Copyright © 2008 eIF2B, composed of five subunits (eIF2Bα, eIF2Bβ, eIF2Bγ, eIF2Bδ, eIF2Bε), is encoded by five different genes (EIF2B1-5) with a total of 57 exons, making gene sequencing expensive and time consuming. Mutations have been found in all five genes and in multiple different exons. 6,25 The great number of individual mutations has confounded efforts at simplifying mutation analysis in suspected eIF2B-related cases, requiring in many cases the sequencing of all five genes to exclude a diagnosis.Efforts to establish a screening tool to streamline the diagnosis of eIF2B-related disorders have included CSF glycine levels, 26 measuring guanine nucleotide exchange factor activity of eIF2B in lymphoblasts (GEF activity), 27 and most recently, decreased CSF asialotransferrin to transferrin ratio. 28 Detection of CSF asialotransferrin to transferrin ratio by 2DG analysis has the advantage of being technologically simple, rapid (<48 hours), inexpensive, and highly sensitive. In this study, we focus on establishing the diagnostic accuracy of 2 DG analysis of CSF asialotransferrin to transferrin ratio for the diagnosis of eIF2B-related disorders. Current diagnosis is based on clinical evaluation followed by confirmation of eIF2B mutation, and this approach will be used as the reference standard. . CSF samples were studied in 60 subjects (figure 1): 6 patient...

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Oligodendrocyte differentiation is increased in transferrin transgenic mice

Cited by 31 publications

References 61 publications

Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes

Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes

Oligodendrocytes and myelination: The role of iron

Sensitivity and specificity of decreased CSF asialotransferrin for eIF2B-related disorder

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