Magnetic resonance microscopy of iron in the basal forebrain cholinergic structures of the aged mouse lemur.

Increased non-heme iron levels in the brain of Alzheimer's disease (AD) patients are higher than the levels observed in age matched normal subjects. Iron level in structures that are highly relevant for AD, such as the basal forebrain, can be detected post mortem with histochemistry. Because of the small size of these structures, in vivo MR detection is very difficult at conventional field magnets (1.5 and 4 T). In this study, we observed iron deposits with histochemistry and MR microscopy at 11.7 T in the brain of the mouse lemur, a strepsirhine primate which is the only known animal model of aging presenting both senile plaques and neurofibrillary degeneration. We also examined a related species, the dwarf lemur. Iron distribution in aged animals (8 to 15 years old) agrees with previous findings in humans. In addition, the high iron levels of the globus pallidus is paralleled by a comparable contrast in basal forebrain cholinergic structures. Because of the enhancement of iron-dependent contrast with increasing field strength, microscopic magnetic resonance imaging of the mouse lemur appears to be an ideal model system for studying in vivo iron changes in the basal forebrain in relation to aging and neurodegeneration.

Topographical localization of lipofuscin pigment in the brain of the aged fat-tailed dwarf lemur (Cheirogaleus medius) and grey lesser mouse lemur (Microcebus murinus): comparison to iron localization.

The present study was undertaken to explore the distribution of lipofuscin in the brain of cheirogaleids by autofluorescence and compare it to other studies of iron distribution. Aged dwarf (Cheirogaleus medius) and mouse (Microcebus murinus) lemurs provide a reliable model for the study of normal and pathological cerebral aging. Accumulation of lipofuscin, an age pigment derived by lipid peroxidation, constitutes the most reliable cytological change correlated with neuronal aging. Brain sections of four aged (8-15 year old) and 3 young (2-3 year old) animals were examined. Lipofuscin accumulation was observed in the aged animals but not in the young ones. Affected regions include the hippocampus (granular and pyramidal cells), where no iron accumulation was observed, the olfactory nucleus and the olfactory bulb (mitral cells), the basal forebrain, the hypothalamus, the cerebellum (Purkinje cells), the neocortex (essentially in the pyramidal cells), and the brainstem. Even though iron is known to catalyse lipid oxidation, our data indicate that iron deposits and lipofuscin accumulation are not coincident. Different biochemical and morphological cellular compartments might be involved in iron and lipofuscin deposition. The nonuniform distribution of lipofuscin indicates that brain structures are not equally sensitive to the factors causing lipofuscin accumulation. The small size, the rapid maturity, and the relatively short life expectancy of the cheirogaleids make them a good model system in which to investigate the mechanisms of lipofuscinogenesis in primates.

Topographical localization of iron in brains of the aged fat-tailed dwarf lemur (Cheirogaleus medius) and gray lesser mouse lemur (Microcebus murinus).

Iron deposits in the human brain are characteristic of normal aging but have also been implicated in various neurodegenerative diseases. Among nonhuman primates, strepsirhines are of particular interest because hemosiderosis has been consistently observed in captive aged animals. In particular, the cheirogaleids, because of their small size, rapid maturity, fecundity, and relatively short life expectancy, are a useful model system for the study of normal and pathological cerebral aging. This study was therefore undertaken to explore iron localization in the brain of aged cheirogaleids (mouse and dwarf lemurs) with histochemistry and magnetic resonance microscopy. Results obtained with both techniques were comparable. There was no difference between old animals in the two species. The young animals (3 years old) showed no iron deposits. In the old animals (8-15 years old), iron pigments were mainly localized in the globus pallidus, the substantia nigra, the neocortical and cerebellar white matter, and anterior forebrain structures, including the nucleus basalis of Meynert. This distribution agrees with previous findings in monkeys and humans. In addition, we observed iron in the thalamus of these aged non-human primates. Microscopic NMR images clearly reveal many features seen with the histochemical procedure, and magnetic resonance microscopy is a powerful method for visualizing age-related changes in brain iron.