Iron Metabolism in Oligodendrocytes and Astrocytes, Implications for Myelination and Remyelination

Abstract

Iron is a key nutrient for normal central nervous system (CNS) development and function; thus, iron deficiency as well as iron excess may result in harmful effects in the CNS. Oligodendrocytes and astrocytes are crucial players in brain iron equilibrium. However, the mechanisms of iron uptake, storage, and efflux in oligodendrocytes and astrocytes during CNS development or under pathological situations such as demyelination are not completely understood. In the CNS, iron is directly required for myelin production as a cofactor for enzymes involved in ATP, cholesterol and lipid synthesis, and oligodendrocytes are the cells with the highest iron levels in the brain which is linked to their elevated metabolic needs associated with the process of myelination. Unlike oligodendrocytes, astrocytes do not have a high metabolic requirement for iron. However, these cells are in close contact with blood vessel and have a strong iron transport capacity. In several pathological situations, changes in iron homoeostasis result in altered cellular iron distribution and accumulation and oxidative stress. In inflammatory demyelinating diseases such as multiple sclerosis, reactive astrocytes accumulate iron and upregulate iron efflux and influx molecules, which suggest that they are outfitted to take up and safely recycle iron. In this review, we will discuss the participation of oligodendrocytes and astrocytes in CNS iron homeostasis. Understanding the molecular mechanisms of iron uptake, storage, and efflux in oligodendrocytes and astrocytes is necessary for planning effective strategies for iron management during CNS development as well as for the treatment of demyelinating diseases.