Isoforms of ferritin have a specific cellular distribution in the brain

Abstract

Ferritin is the major iron storage protein and accounts for the majority of the iron in the brain. Thus, ferritin is a key component in protecting the brain from iron induced oxidative damage. The high lipid content, high rate of oxidative metabolism, and high iron content combine to make the brain the organ most susceptible to oxidative stress. The role of oxidative damage and disruption of brain iron homeostasis is considered clinically important to normal aging and a potential pathogenic component of a number of neurologic disorders including Alzheimer's disease and Parkinson's disease. Little is known, however, of the mechanism by which the brain maintains iron homeostasis at either the whole organ or cellular level. In this study we report the cellular distribution of the two isoforms of ferritin in the brain of adult subhuman primates. A subset of neurons immunolabel specifically for the H-chain ferritin protein, whereas cells resembling microglia are immunolabeled only after exposure to the L-chain ferritin antibody. Only one cell type immunostains for both H- and L-chain ferritin; these cells are morphologically similar and have the same distribution pattern as oligodendrocytes. Neither ferritin isoform is usually detected in astrocytes. These data indicate considerable differences in iron sequestration and use between neurons and glia and among neuronal and glial subtypes. This information will be essential in determining the role of each of these cells in maintaining general brain iron homeostasis and the relative abilities of these cells to withstand oxidative stress.