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

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).

Oligodendrogenesis: the role of iron.

Iron seems to be an essential factor in myelination and oligodendrocyte (OLGc) biology. However, the specific role of iron in these processes remains to be elucidated. Iron deficiency (ID) imposed to developing rats has been a relevant model to understand the role of iron in oligodendrogenesis and myelination. During early development ID causes specific changes in myelin composition, including a lower relative content of cholesterol, proteolipid protein (PLP), and myelin basic protein 21 (MBP21). These changes could be a consequence of the adverse effects of ID on OLGc development and function. We subsenquently studied the possible corrective effect of a single intracranial injection (ICI) of apotransferrin (aTf) on myelin formation in ID rats OLGc migration and differentiation after an ICI of aTf was evaluated at 3 days of age. ID increased the number of proliferating and undifferentiated cells in the corpus callosum (CC), while a single aTf injection reverts these effects, increasing the number of mature cells and myelin formation. Overall, results of a series of studies supports the concept that iron may affect OLGc development at early stages of embryogenesis rather than during late development. Myelin composition is altered by a limited iron supply, changes that can be reverted by a single injection of aTf.