Abstract
A subpopulation of neurons is less vulnerable against iron-induced oxidative stress and neurodegeneration. A key feature of these neurons is a special extracellular matrix composition that forms a perineuronal net (PN). The PN has a high affinity to iron, which suggests an adapted iron sequestration and metabolism of the ensheathed neurons. Highly active, fast-firing neurons—which are often ensheathed by a PN—have a particular high metabolic demand, and therefore may have a higher need in iron. We hypothesize that PN-ensheathed neurons have a higher intracellular iron concentration and increased levels of iron proteins. Thus, analyses of cellular and regional iron and the iron proteins transferrin (Tf), Tf receptor 1 (TfR), ferritin H/L (FtH/FtL), metal transport protein 1 (MTP1 aka ferroportin), and divalent metal transporter 1 (DMT1) were performed on Wistar rats in the parietal cortex (PC), subiculum (SUB), red nucleus (RN), and substantia nigra (SNpr/SNpc). Neurons with a PN (PN+) have higher iron concentrations than neurons without a PN: PC 0.69 mM vs. 0.51 mM, SUB 0.84 mM vs. 0.69 mM, SN 0.71 mM vs. 0.63 mM (SNpr)/0.45 mM (SNpc). Intracellular Tf, TfR and MTP1 contents of PN+ neurons were consistently increased. The iron concentration of the PN itself is not increased. We also determined the percentage of PN+ neurons: PC 4%, SUB 5%, SNpr 45%, RN 86%. We conclude that PN+ neurons constitute a subpopulation of resilient pacemaker neurons characterized by a bustling iron metabolism and outstanding iron handling capabilities. These properties could contribute to the low vulnerability of PN+ neurons against iron-induced oxidative stress and degeneration.
Highlights
Introduction published maps and institutional affilNo other organ than the brain constantly needs readily available iron in a regional, cellular and age-dependent manner [1]
The quantitative element maps, that were obtained by μPIXE analysis (Figure 1), allow to identify the regions of interest (ROIs), perineuronal net (PN)+ and PN– neurons as well as the PN, and to extract the average iron concentrations therein
The results merely suggest that PN+ neurons have generally a higher cytochrome c oxidase activity, but corroborate the conclusion of an increased energy metabolism of PN+ neurons that were drawn from the analyses of the cellular iron and iron protein contents
Summary
No other organ than the brain constantly needs readily available iron in a regional, cellular and age-dependent manner [1]. A failure to meet this demand for iron can result in persistent neurological and cognitive dysfunction [1]. On the other hand, increased iron levels and iron accumulations in specific brain regions and cells are hallmarks for more than 15 neurodegenerative diseases including. Iron accumulates as a normal process of aging. This is caused by a slow brain iron turnover and an influx being higher than the efflux. This process was investigated in a longterm-study on healthy rats [7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
