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SHR Neuro Cancer Cardio Lipid Metab Microb

Sunkara, S; Radulović, S; Lipovšek, S; Birkl, C; Eggenreich, S; Birkl-Toeglhofer, AM; Schinagl, M; Funk, D; Stöger-Pollach, M; Haybaeck, J; Goessler, W; Ropele, S; Leitinger, G.
Autolysis Affects the Iron Cargo of Ferritins in Neurons and Glial Cells at Different Rates in the Human Brain.
Cell Mol Neurobiol. 2023; 43(6):2909-2923 Doi: 10.1007/s10571-023-01332-w [OPEN ACCESS]
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Leading authors Med Uni Graz
Leitinger Gerd
Radulovic Snjezana
Sunkara Sowmya
Co-authors Med Uni Graz
Birkl Christoph
Birkl-Töglhofer Anna Maria
Eggenreich Stefan
Haybäck Johannes
Lipovsek Saska
Ropele Stefan
Schinagl Maximilian
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Abstract:
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.
Find related publications in this database (using NLM MeSH Indexing)
Humans - administration & dosage
Iron - metabolism
Ferritins - metabolism
Neuroglia - metabolism
Neurons - metabolism
Brain - metabolism

Find related publications in this database (Keywords)
Ferritin
Human brain
Energy-filtered transmission electron microscopy
Quantitative magnetic resonance imaging
Inductively coupled plasma mass spectrometry
Autolysis
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