RELATIONSHIP OF IRON TO OLIGODENDROCYTES AND MYELINATION

Oligodendrocytes are the predominant iron-containing cells in the brai n. Iron-containing oligodendrocytes are found near neuronal cell bodie s, along blood vessels, and are particularly abundant within white mat ter tracts. Iron-positive cells in white matter are present from birth and eventually reside in defined patches of cells in the adult. These patches of iron-containing cells typically have a blood vessel in the ir center. Ferritin, the iron storage protein, is also expressed early in development in oligodendrocytes in a regional and cellular pattern similar to that seen for iron. Recently, the functionally distinct su bunits of ferritin have been analyzed; only heavy (H)-chain ferritin i s found in oligodendrocytes early in development. H-ferritin is associ ated with high iron utilization and low iron storage. Consistent with the expression of H-ferritin is the expression of transferrin receptor s (for iron acquisition) on immature oligodendrocytes. Transferrin pro tein accumulation and mRNA expression in the brain are both dependent on a viable population of oligodendrocytes and may have an autocrine f unction to assist oligodendrocytes in iron acquisition. Although appar ently the majority of oligodendrocytes in white matter tracts contain ferritin, transferrin, and iron, not all of them do, indicating that t here is a subset of oligodendrocytes in white matter tracts. The only known function of oligodendrocytes is myelin production, and both a di rect and indirect relationship exists between iron acquisition and mye lin production. Iron is directly involved in myelin production as a re quired co-factor for cholesterol and lipid biosynthesis and indirectly because of its requirement for oxidative metabolism (which occurs in oligodendrocytes at a higher rate than other brain cells). Factors (su ch as cytokines) and conditions such as iron deficiency may reduce iro n acquisition by oligodendrocytes and the susceptibility of oligodendr ocytes to oxidative injury may be a result of their iron-rich cytoplas m. Thus, the many known phenomena that decrease oligodendrocyte surviv al and/or myelin production may mediate their effect through a final c ommon pathway that involves disruptions in iron availability or intrac ellular management of iron. (C) 1996 Wiley-Liss, Inc.