Accumulation of Non-Transferrin-Bound Iron by Neurons, Astrocytes, and Microglia
Iron is found in high concentration in some areas of the brain, and increased iron in the substantia nigra is a feature of Parkinson's disease. The purpose of this study was to investigate the physical environment of brain iron in post-mortem tissue to provide information on the possible role of iron in neurodegeneration in Parkinson's disease. Iron has also been implicated as the cause of signal loss in areas of high brain iron on T2-weighted MRI sequences. Knowledge of the physical environment of the brain iron is essential in interpreting the cause of signal change. Post-mortem tissue was obtained from six cases of Parkinson's disease and from six age-matched controls. Iron levels were measured using absorption spectrophotometry. Extended X-ray absorption fine structure was used to evaluate the atomic environment of iron within the substantia nigra and both segments of the globus pallidus. Cryo-electron transmission microscopy was used to probe the iron storage proteins in these areas. Iron levels were increased in the parkinsonian nigra and lateral portion of the globus pallidus. Spectra from the extended X-ray absorption fine structure experiments showed that ferritin was the only storage protein detectable in both control and parkinsonian tissue in all areas studied. Cryo-electron transmission microscopy studies showed that ferritin was more heavily loaded with iron in Parkinson's disease when compared with age-matched controls. In summary we have shown that iron levels are increased in two areas of the brain in Parkinson's disease including the substantia nigra, the site of maximal neurodegeneration. This produces increased loading of ferritin, which is the normal brain iron storage protein. It is possible that increased loading of ferritin may increase the risk of free radical-induced damage. Differences in ferritin loading may explain regional differences in iron's effect on the T2 signal.