Cellular distribution of transferrin, ferritin, and iron in normal and aged human brains

Abstract

The iron transport protein, transferrin, and the iron storage protein ferritin were examined immunohistochemically along with iron in a number of brain regions from normal and aged humans. Two age groups were examined: a middle-aged group (28-49 years), and an older group (60-90 years). Transferrin, ferritin, and iron are found throughout all brain regions examined, predominantly in the perikaryal cytoplasm of cells that are small and round, fitting the description of oligodendrocytes. These cells are present in the optic nerve and in both the gray and white matter of the cerebral cortex, cerebellum, and olfactory bulb in both age groups. Ferritin is also found in microglial cells in the gray matter of most of these brain regions. In the subcortical regions examined (corpus striatum, hippocampus, amygdala), in addition to oligodendrocytes, astrocytes can frequently be observed that contain transferrin, ferritin, and iron. There is an age-related alteration in cell labeling: astrocytes in both gray and white matter contained transferrin in the oldest age group, whereas in the younger group the subcortical transferrin immunoreactivity was confined mostly to oligodendrocytes. Ferritin in the subcortical brain regions is also present in astrocytes but is primarily confined to those in the gray matter, even in the oldest age group. Iron is found predominantly in oligodendrocytes, although a few iron-positive astrocytes and microglia can be identified. These results indicate that (1) normally oligodendrocytes contain much of the iron and iron-binding proteins found in the brain; and (2) an increase in age is associated with altered cellular distribution of iron-binding proteins, but the altered distribution is specific to glial cells. These results suggest glial cells may have previously undescribed functions related to metal regulation and sequestration.

Mitochondrial Iron Sequestration in Dopamine‐Challenged Astroglia: Role of Heme Oxygenase‐1 and the Permeability Transition Pore

“…The latter promote further oxidative stress, thereby amplifying damage to vulnerable glial and neuronal constituents within the PD nigra (Schipper, 1996;Frankel and Schipper, 1997). Our model for pathological iron sequestration in PD-affected neural tissues is consistent with reports that a significant proportion of the excess iron in PD brain may indeed be localized to astroglial mitochondria (Connor et al, 1990;Jellinger et al, 1990;Olanow, 1992), deficiencies of mitochondrial electron transport are prevalent in the brains of PD subjects (Reichmann and Riederer, 1994;Beal, 1995), and the percentage of glial fibrillary acidic protein-positive astrocytes expressing immunoreactive HO-1 in substantia nigra of PD subjects is significantly increased in comparison with age-matched controls (Schipper et al, 1998).…”

Cellular and subcellular localizations of nonheme ferric and ferrous iron in the rat brain: a light and electron microscopic study by the perfusion-Perls and -Turnbull methods

“…Fe(III) and Fe(II), are extensively distributed throughout the brain, are especially highly concentrated in the diencephalon, basal ganglia, brain stem, and cerebellum, s i m i l a r t o p r e v i o u s o b s e r v a t i o n s f o r F e ( I I I ) i n various mammalian and human brains (Hill and Switzer, 1984;Connor et al, 1990;Morris et al, 1992;Gilissen et al, 1998).…”

Iron chelation in the treatment of neurodegenerative diseases

“…Microglia and macrophages may serve as iron donors for oligodendrocytic progenitor cells which are responsible for remyelination [165,166]. On the other hand, excessive iron concentration in macrophages may promote a pro-inflammatory M1 activation state and facilitate inflammation [167].…”