Changes in cellular ferritin distribution of human brain tissue during autolysis revealed using analytical electron microscopy

Iron in the human brain is stored in the cores of ferritin proteins. Excess iron has been implicated in neurological disorders, so a careful balance of the iron concentration is thought to be essential for human health. Though it is known that oligodendrocytes contain most of the brain ferritin, followed by other glial cells and neurons, little is known about changes in the cellular ferritin distribution when total iron load changes. Moreover, changes in the number of filled ferritins or in their cellular distribution during autolysis have not been revealed yet. To reveal these changes, we examined brain samples taken from six deceased humans at different post mortem times. To compare samples with different ferritin content, the samples included the frontal gray and frontal white matter, which store a low amount of iron, and the putamen and globus pallidus, which store a high amount of iron. We quantified the number of loaded ferritin cores from iron L - elemental maps obtained with energy filtered transmission electron microscopy and compared this number to the iron concentrations determined using inductively coupled plasma mass spectrometry and quantitative magnetic resonance imaging. The more loaded ferritin cores we found in the tissues, the higher the proportion of ferritins found in neurons instead of glial cells, indicating that total ferritin load scales with the proportion of ferritin that is located in neurons. Second, we found a statistically significant correlation between the post mortem interval and the amount / concentration of loaded ferritins and found that this concentration is highly dependent on the post mortem interval (PMI): the longer the PMI, the lower the ferritin concentration found in a sample. Third, the longer the post mortem interval, the higher the proportion of ferritins found in neurons instead of glial cells, indicating that ferritin loss during autolysis affects neurons and glial cells at different rates. ### Competing Interest Statement The authors have declared no competing interest.