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.