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

Abstract

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).

Environmental Cues Modulate Microglial Cell Behavior Upon Shiga Toxin 2 From Enterohemorrhagic Escherichia coli Exposure

“…Total brains of post-natal day (P) 0-1 Wistar rat pups from both sex (8-10 animals/litter) were dissected and plated on T75 polylysinated flasks and cultured in Dulbecco's Modified Eagle's medium (DMEM) supplemented with F12 (DMEM/F12) and 10% fetal calf serum (FCS) for 11-13 days. Following the original protocol (de Vellis and Cole, 2012;Rosato-Siri et al, 2018), MG cells were obtained by differential centrifugation and plated on uncoated surfaces, suitable for the subsequent assay (Figure 1). MG cells culture purity (CD11b positive cells) was checked regarding neuron, oligodendrocytes and astrocytes contamination by NeuN, O4, and GFAP ICC, respectively, rendering 98% pure MG cells cultures (data not shown).…”

“…Immunocytochemistry (ICC) was performed as previously described (Rosato-Siri et al, 2018). Briefly, covers were washed with phosphate buffered saline (PBS), permeabilized (PBS + 0.1% Triton X-100 + 5% FCS) for 3 h and sequentially exposed to primary antibodies (PBS + 0.1% Triton X-100 + 1% FCS) and secondary antibodies (PBS + 0.1% Triton X-100 + 1% FCS) ( Table 2).…”

The Effects of Prenatal Iron Deficiency and Risperidone Treatment on the Rat Frontal Cortex: A Proteomic Analysis

“…In parallel, risperidone acted to decrease markers of OS by manipulating antioxidative enzymes. Recent studies from our group have demonstrated that microglial cultures derived from ID animals exhibit poor inflammatory potential . On the basis of these parallel findings, more thorough bioassays will be carried out to study risperidone's effects in the ID model.…”

Analysis of the Direct and Indirect Effects of Nanoparticle Exposure on Microglial and Neuronal Cells In Vitro

“…Iron is an important cofactor in several enzymes, including enzymes involved in myelin production and maintenance and mitochondrial oxidative metabolism. As such it plays an important role in cell proliferation, metabolism and differentiation [ 45 , 46 ]. While lower increase in iron concentration might thus have a stimulatory effect on cell proliferation, as observed also in our study, higher concentrations still induce toxicity and possibly neurodegeneration [ 47 , 48 ].…”