Oligodendrocytes: Functioning in a Delicate Balance Between High Metabolic Requirements and Oxidative Damage

The study of the metabolic interactions between myelinating glia and the axons they ensheath has blossomed into an area of research much akin to the elucidation of the role of astrocytes in tripartite synapses (Tsacopoulos and Magistretti in J Neurosci 16:877-885, 1996). Still, unlike astrocytes, rich in cytochrome-P450 and other anti-oxidative defense mechanisms (Minn et al. in Brain Res Brain Res Rev 16:65-82, 1991; Wilson in Can J Physiol Pharmacol. 75:1149-1163, 1997), oligodendrocytes can be easily damaged and are particularly sensitive to both hypoxia and oxidative stress, especially during their terminal differentiation phase and while generating myelin sheaths. In the present review, we will focus in the metabolic complexity of oligodendrocytes, particularly during the processes of differentiation and myelin deposition, and with a specific emphasis in the context of oxidative stress and the intricacies of the iron metabolism of the most iron-loaded cells of the central nervous system (CNS).