Autolysis Affects the Iron Cargo of Ferritins in Neurons and Glial Cells at Different Rates in the Human Brain.

Autor: Sunkara S; Gottfried Schatz Research Center, Division of Cell Biology, Histology and Embryology, Research Unit Electron Microscopic Techniques, Medical University of Graz, 8010, Graz, Austria., Radulović S; Gottfried Schatz Research Center, Division of Cell Biology, Histology and Embryology, Research Unit Electron Microscopic Techniques, Medical University of Graz, 8010, Graz, Austria. snjezana.radulovic@medunigraz.at., Lipovšek S; Gottfried Schatz Research Center, Division of Cell Biology, Histology and Embryology, Research Unit Electron Microscopic Techniques, Medical University of Graz, 8010, Graz, Austria.; Faculty of Medicine, University of Maribor, 2000, Maribor, Slovenia.; Department of Biology, Faculty of Natural Sciences and Mathematics, University of Maribor, 2000, Maribor, Slovenia.; Faculty of Chemistry and Chemical Engineering, University of Maribor, 2000, Maribor, Slovenia., Birkl C; University Clinic for Neuroradiology, Medical University of Innsbruck, 6020, Innsbruck, Austria., Eggenreich S; Neuroimaging Research Unit, Department of Neurology, Medical University of Graz, 8010, Graz, Austria., Birkl-Toeglhofer AM; Institute for Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, 6020, Innsbruck, Austria., Schinagl M; Gottfried Schatz Research Center, Division of Cell Biology, Histology and Embryology, Research Unit Electron Microscopic Techniques, Medical University of Graz, 8010, Graz, Austria.; Institute of Chemical Technologies and Analytics, Technische Universität Wien, 1040, Vienna, Austria.; Diagnostic and Research Center for Molecular BioMedicine, Institute of Pathology, Medical University of Graz, 8010, Graz, Austria., Funk D; Gottfried Schatz Research Center, Division of Cell Biology, Histology and Embryology, Research Unit Electron Microscopic Techniques, Medical University of Graz, 8010, Graz, Austria., Stöger-Pollach M; University Service Centre for Transmission Electron Microscopy (USTEM), Technische Universität Wien, 1040, Vienna, Austria., Haybaeck J; Institute for Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, 6020, Innsbruck, Austria.; Diagnostic and Research Center for Molecular BioMedicine, Institute of Pathology, Medical University of Graz, 8010, Graz, Austria., Goessler W; Institute for Chemistry, University of Graz, 8010, Graz, Austria., Ropele S; Neuroimaging Research Unit, Department of Neurology, Medical University of Graz, 8010, Graz, Austria., Leitinger G; Gottfried Schatz Research Center, Division of Cell Biology, Histology and Embryology, Research Unit Electron Microscopic Techniques, Medical University of Graz, 8010, Graz, Austria.
Jazyk: angličtina
Zdroj: Cellular and molecular neurobiology [Cell Mol Neurobiol] 2023 Aug; Vol. 43 (6), pp. 2909-2923. Date of Electronic Publication: 2023 Mar 15.
DOI: 10.1007/s10571-023-01332-w
Abstrakt: Iron is known to accumulate in neurological disorders, so a careful balance of the iron concentration is essential for healthy brain functioning. An imbalance in iron homeostasis could arise due to the dysfunction of proteins involved in iron homeostasis. Here, we focus on ferritin-the primary iron storage protein of the brain. In this study, we aimed to improve a method to measure ferritin-bound iron in the human post-mortem brain, and to discern its distribution in particular cell types and brain regions. Though it is known that glial cells and neurons differ in their ferritin concentration, the change in the number and distribution of iron-filled ferritin cores between different cell types during autolysis has not been revealed yet. Here, we show the cellular and region-wide distribution of ferritin in the human brain using state-of-the-art analytical electron microscopy. We validated the concentration of iron-filled ferritin cores to the absolute iron concentration measured by quantitative MRI and inductively coupled plasma mass spectrometry. We show that ferritins lose iron from their cores with the progression of autolysis whereas the overall iron concentrations were unaffected. Although the highest concentration of ferritin was found in glial cells, as the total ferritin concentration increased in a patient, ferritin accumulated more in neurons than in glial cells. Summed up, our findings point out the unique behaviour of neurons in storing iron during autolysis and explain the differences between the absolute iron concentrations and iron-filled ferritin in a cell-type-dependent manner in the human brain. The rate of loss of the iron-filled ferritin cores during autolysis is higher in neurons than in glial cells.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: