Molecular Neurobiology

, Volume 55, Issue 2, pp 1068–1081 | Cite as

Iron Availability Compromises Not Only Oligodendrocytes But Also Astrocytes and Microglial Cells

  • Maria Victoria Rosato-Siri
  • Leandro Marziali
  • María Eugenia Guitart
  • Maria Elvira Badaracco
  • Mariana Puntel
  • Fernando Pitossi
  • Jorge Correale
  • Juana Maria Pasquini


When disrupted, iron homeostasis negatively impacts oligodendrocyte (OLG) differentiation and impairs myelination. To better understand myelin formation and OLG maturation, in vivo and in vitro studies were conducted to evaluate the effect of iron deficiency (ID) not only on OLG maturation but also on astrocytes (AST) and microglial cells (MG). In vivo experiments in an ID model were carried out to describe maturational events during OLG and AST development and the reactive profile of MG during myelination when iron availability is lower than normal. In turn, in vitro assays were conducted to explore proliferating and maturational states of each glial cell type derived from control or ID conditions. Studies targeted NG2, PDGFRα, CNPAse, CC1, and MBP expression in OLG, GFAP and S100 expression in AST, and CD11b, ED1, and cytokine expression in MG, as well as BrDU incorporation in the three cell types. Our results show that ID affected OLG development at early stages, not only reducing their maturation capacity but also increasing their proliferation and affecting their morphological complexity. AST ID proliferated more than control ones and were more immature, much like OLG. Cytokine expression in ID animals reflected an anti-inflammatory state which probably influenced OLG maturation. These results show that ID conditions alter all glial cells and may impact myelin formation, which could be regulated by a mechanism involving a cross talk between AST, MG, and oligodendrocyte progenitors (OPC).


Iron deficiency Oligodendrocyte maturation Astrocyte response Microglial cell activation Hypomyelination 



This work was supported by generous funding from Universidad de Buenos Aires; grant number: 20020100100395. We are especially grateful to Marianela Vence for her special dedication and technical assistance with experimental animals and to María Marta Rancez for her helpful insights.

Compliance with Ethical Standards

Conflict of Interest

The authors have no conflict of interest to declare.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Maria Victoria Rosato-Siri
    • 1
  • Leandro Marziali
    • 1
  • María Eugenia Guitart
    • 1
  • Maria Elvira Badaracco
    • 1
  • Mariana Puntel
    • 2
  • Fernando Pitossi
    • 2
  • Jorge Correale
    • 3
  • Juana Maria Pasquini
    • 1
  1. 1.Departamento de Química Biológica, Facultad de Farmacia y Bioquímica. IQUIFIB-CONICETUniversidad de Buenos AiresBuenos AiresArgentina
  2. 2.Instituto Leloir - IIBBA-CONICETBuenos AiresArgentina
  3. 3.Instituto de Investigaciones Neurológicas Dr. Raúl Carrea, FLENIBuenos AiresArgentina

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