Iron deposit induced oxidative stress in substantia nigra of aged rats

Background: The excessive deposit of iron in glial cell of some intracerebral areas and iron-induced oxidative stress might be related with the onset of some neurodegenerative diseases, such as Parkinson disease(PD). However, there are not many objective evaluative criteria for the researches on the sub-cellularity of iron deposit in the midbrain substantia nigra(SN) in F344 elder rats at present. Objective: To observe the iron deposit in SN part of F344 elder rats to provide theoretic gist for further understanding of PD pathogenesis. Design: A randomized controlled trial. Setting: Beijing institute of Neuroscience, Capital Medical University, Department of Anatomy and Neurobiology, University of Kentucky, College of Medicine, Lexinton. Materials: Six 24-month old and four 3-month old Fischer(F344) male rats were selected. Interventions: Brain tissues were harvested after perfusion fixation for the removal of midbrain part, which would be sliced into 40 μm brain slice on oscillating microtome. Techniques like immunohistochemistry, confocal laser scanning microscope, transmission electron microscope and electronprobe elementary microanalysis, etc. were employed for a systemic histochemical and morphologic observation on iron deposit in midbrain SN site. Main outcome measures: Iron deposit in midbrain SN site was observed under optical microscope, confocal laser scanning microscope and transmission electron microscope and analyzed by electroprobe elementary microanalysis. Results: Under optical microscope, Ferritin, the major storage mode of iron, was significantly increased in SN reticular area, which was also increased with the increase of microglia. Under confocal laser scanning microscope, it was observed that Ferritins were very few in dopaminergic neurons and astrocytes but mostly in microglia. The results of electroprobe analysis indicated that free iron mainly in the cytoplasm of astrocyte, which was also in microglia, oligodendroglia and some neuronal cytoplasm. Conclusion: The increase of microglia with the increase of the age in SN might be one of the reasons of iron deposit in SN, and the oxidative injury in elder nervous system induced by the increase of free radicles caused by the latter might be one of important intrinsic factors causing the increase of PD incidence in the elderly population.