Search

The role of iron in pathogenesis of Parkinson's disease is widely discussed in the literature. The authors present the history of studies of iron in parkinsonian tissue from the substantia nigra.

The aim of the present study was to assess the origin of the substantia nigra hyperechogenicity in Parkinson disease patients. The cause of hyperechogenicity was tested on an animal model. Fresh porcine brains were injected consecutively with ferritin, apoferritin and water. Then, glioma samples were inserted into animal model. The echogenicity of the region of interest was assessed before and after experimental procedures. We observed the same echogenicity of porcine brain before and after injections of iron-loaded ferritin, apoferritin and water. Increased echogenicity of glioma samples compared to surrounding porcine brain tissue could be clearly seen. We postulate that the relative gliosis might be, at least partially, responsible for the increased echogenicity of the substantia nigra in Parkinson disease patients. Keeping in mind all limitations and inaccuracies of animal model used, it seems that hyperechogenicity of substantia nigra is caused rather by structural changes within the brain tissue than by increased iron concentration.

Objectives: We sought to determine concentrations of total and labile iron in substantia nigra from patients with Parkinson disease and from controls to assess if oxidative stress is triggered by an increased concentration of iron., Methods: Total iron concentration in the whole substantia nigra was evaluated in 17 parkinsonian and 29 control samples. Concentrations of labile iron and copper were assessed in 6 parkinsonian and 8 control samples. The total iron concentration, the Fe(2+)/Fe(3+) ratio, and iron-binding compounds were determined by Mössbauer spectroscopy. Labile iron and copper were measured by electrothermal atomic absorption spectrometry. Activity of reactive oxygen species was evaluated by visible light fluorescence., Results: The labile iron concentration was significantly higher and corresponded to significantly higher reactive oxygen species activity in parkinsonian vs control samples. No significant difference was found in the total concentrations of copper or iron in the whole substantia nigra between parkinsonian and control samples. Mössbauer spectroscopy detected no Fe(2+) in any samples., Conclusions: The substantia nigra of parkinsonian patients contained more labile iron compared with that of controls. This labile iron generated higher reactive oxygen species activity. The oxidative stress damage in parkinsonian substantia nigra may be related to an excess of labile iron and not of the total iron in the diseased tissue.

Iron released from ferritin may trigger oxidative stress leading to progressive neurodegeneration of substantia nigra resulting in Parkinson's disease (PD). Change in the structure of ferritin may allow an easier efflux of iron. We compared with the use of ELISA the structure of ferritin (concentrations of H and L ferritins) in substantia nigra (SN) in ten cases of PD, six of incidental Lewy body (ILB) cases and 20 controls. SN concentration of L ferritin in ILB (50.6+/-11.5 ng/mg) and in PD (52.5+/-26.0) was lower than in control (97.9+/-54.9). H ferritin in PD (534.2+/-223.1) was higher than in ILB (336.9+/-87.7) and control (374.8+/-169.3). The decrease of L ferritin in SN in PD and ILB may suggest that the whole process of neurodegeneration starts with a higher availability of free iron, which is released from the ferritin shell.

The concentrations of iron and of ferritin, the main iron-binding compound in the brain, as well as the sizes of the iron cores of ferritin were assessed in hippocampal cortex (Hip) and substantia nigra (SN) from human control brains, using Mössbauer spectroscopy (MS), ELISA and electron microscopy. 8 Hip and 20 SN samples were measured by MS, 11 Hip and 11 SN were used for ELISA, and the size of the iron cores of ferritin was assessed from measurements of 50 iron cores from Hip-ferritin and 50 iron cores from SN-ferritin. The average concentration of iron in Hip was found to be about one third of that in SN, as was the concentration of H-ferritin, yet L-ferritin was less than one fifth in Hip compared to SN. The size of the average iron core in Hip was assessed to be about 3.1 nm and about 3.7 nm in SN. These results may point to different iron metabolism in these areas, suggesting faster iron turnover in Hip.

The possible role of iron in the degeneration of nervous cells in Parkinson's disease (PD) was studied with the use of Mössbauer spectroscopy (MS) and enzyme-linked immunoabsorbent assay (ELISA). Mössbauer data were obtained at 90 and 4.1 K from 21 samples of control and 9 samples of parkinsonian substantia nigra (SN). Mössbauer spectra were very similar to those observed in ferritin. Small differences were detected between the spectra obtained from PD and from control SN, and could be due to a slight difference in the composition of the ferritin-like iron cores or due to the presence of about 8% of non-ferritin-like iron in parkinsonian SN. ELISA studies from 11 controls and 6 parkinsonian SN showed a decrease in the concentration of L-chains in wet tissues of PD-SN compared to control SN. The decrease in the amount of L subunits may correspond to a decreased ability of this ferritin to keep iron in a safe form. Iron released from ferritin or neuromelanin (NM) may be the source of such iron, which may cause the difference in the Mössbauer spectra and may trigger oxidative stress leading to cell death.

The results of our studies of iron in three brain structures, substantia nigra (SN), globus pallidus (GP), and hippocampus (Hip), are presented. Mössbauer spectroscopy, electron microscopy and ELISA (enzyme-linked immuno-absorbent assay) were applied. Mössbauer studies show that most of the iron in the brain is ferritin-like. The concentration of iron is similar in SN and GP, but less than half of this in Hip. ELISA studies showed that the H/L ratio of ferritin in SN and GP is also similar, but is about three times higher in Hip. These results suggest that the role of iron in SN and GP may be different from that in Hip. Electron microscopy shows that the diameters of the ferritin iron cores in the brain are smaller that in the liver (3.5 ± 0.5 nm vs. 6.0 ± 0.5 nm). Mössbauer studies yield the ratio between the concentration of iron in control and parkinsonian SN as 1.00 ± 0.13. [ABSTRACT FROM AUTHOR]

Accumulating data confirm the usefulness of transcranial sonography (TCS) in the diagnosis of Parkinson's disease. The relevance of basal ganglia abnormalities depicted by TCS in atypical parkinsonian syndromes still needs further assessment. In the present study, 20 patients with progressive supranuclear palsy (PSP) and 13 patients with corticobasal syndrome (CBS) were studied with the use of transcranial sonography. Echogenicity of the substantia nigra (SN) and lenticular nucleus (LN) were assessed. 0/20 patients with PSP and 8/12 (66.6 %) patients with CBS were characterized with SN hyperechogenicity. LN hyperechogenicity was observed in 9/20 patients diagnosed with PSP and 0/11 of CBS patients. The combination of SN isoechogenicity and LN hyperechogenicity reached 100 % sensitivity and positive predictive value for the diagnosis of PSP. The results of this study point out that CBS has to be taken into consideration when SN hyperechogenicity is depicted in a patient with parkinsonian syndrome. Normal echogenicity of the SN coexisting with LN hyperechogenicity practically excludes CBS. [ABSTRACT FROM AUTHOR]

Summary: Iron is considered to be a possible trigger of oxidative stress leading to neurodegeneration. This mechanism of neuronal death is proposed as a cause of Parkinson disease. Although most of researchers agree with this, controversies remain regarding the amounts of iron needed for this process. According to non destructive methods of assessment of the concentration of the total iron in substantia nigra, there is no difference between PD and control. However there is no need for an increase of the total iron in parkinsonian SN to trigger the oxidative stress but only of the non-ferritin bound labile iron. Our recent studies suggest an increase of this iron in PD SN. This finding corresponds well to a decrease of L-ferritin concentration in parkinsonian SN and also to a difference of the size of iron core of ferritin between PD and control SN. The significance of these finding will be discussed. [Copyright &y& Elsevier]