Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Sele, M.
Iron deposits in the human post-mortem brain: An electron microscopic study.
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2020. pp. 138
[OPEN ACCESS]
FullText
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Khalil Michael
- Leitinger Gerd
- Ropele Stefan
- Altmetrics:
- Abstract:
- Iron is crucial for the human body as it is used for various important processes like oxygen transport, mitochondrial energy generation, or myelin and neurotransmitter synthesis. Furthermore, iron is associated with many neurodegenerative and inflammatory diseases, where an altered iron metabolism may play a role. In addition, it is known that during brain aging, iron accumulates in distinct regions which are associated with Alzheimer’s disease and Parkinson’s disease. Ferritin is the major iron storage protein in the human body and is mostly localised in liver and spleen but also in the heart and the brain. The ferritin particle consists of a globular shell formed by ferritin proteins and an iron core which encloses up to a few thousands iron atoms. The aim of this study was to research the cellular and subcellular distribution of ferritin, specifically its iron core, in the human brain in health and disease, respectively. More knowledge about the cellular distribution of iron in the human brain may provide more insight into the mechanics which underlie these debilitating diseases. Electron microscopy can provide the necessary resolution to localise ferritin particles in brain tissue. With energy-filtered transmission electron microscopy (EFTEM), the iron core of the ferritin particles can be visualised in the sample slice. These findings can be compared with the total amount of iron of the individual brain regions determined by mass spectrometry (MS). In a first step, the sample preparation was optimised regarding a better preservation of the ultrastructure of the tissue showing signs of degradation by autolytic processes. Therefore, a new preparation method, the hybrid freezing method, was established. On average, in the frontal cortex, an iron particle concentration of 55.6 and in its corresponding white matter 16.9 iron particles per cubic micrometre could be observed. In the basal ganglia, higher amounts of 208.7 iron particles per cubic micrometre in the putamen and 149.7 in the globus pallidus, respectively, were found. The iron scores of the analysed brain region determined with EFTEM correlate with the results obtained by mass spectrometry if only the mean values are taken into account. A correlation of MS results with the EFTEM iron values was difficult to reach due to the high range of observational errors of the methods. The number of samples examined was too small to draw any relevant conclusions regarding an altered iron metabolism in Alzheimer’s disease. Further investigations with a greater samples size, for both healthy and diseased individuals, are important to gain more knowledge about the distribution and metabolism of iron in the human brain.