date: 2022-02-09T02:30:13Z pdf:unmappedUnicodeCharsPerPage: 17 pdf:PDFVersion: 1.7 pdf:docinfo:title: High Iron and Iron Household Protein Contents in Perineuronal Net-Ensheathed Neurons Ensure Energy Metabolism with Safe Iron Handling xmp:CreatorTool: LaTeX with hyperref Keywords: brain; iron; iron proteins; perineuronal net; neurodegeneration; transferrin; transferrin receptor; ferritin H/L; DMT1; MTP1; cellular quantification access_permission:modify_annotations: true access_permission:can_print_degraded: true subject: 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. dc:creator: Firstname Lastname, Firstname Lastname and Firstname Lastname dcterms:created: 2022-02-09T02:21:31Z Last-Modified: 2022-02-09T02:30:13Z dcterms:modified: 2022-02-09T02:30:13Z dc:format: application/pdf; version=1.7 title: High Iron and Iron Household Protein Contents in Perineuronal Net-Ensheathed Neurons Ensure Energy Metabolism with Safe Iron Handling Last-Save-Date: 2022-02-09T02:30:13Z pdf:docinfo:creator_tool: LaTeX with hyperref access_permission:fill_in_form: true pdf:docinfo:keywords: brain; iron; iron proteins; perineuronal net; neurodegeneration; transferrin; transferrin receptor; ferritin H/L; DMT1; MTP1; cellular quantification pdf:docinfo:modified: 2022-02-09T02:30:13Z meta:save-date: 2022-02-09T02:30:13Z pdf:encrypted: false dc:title: High Iron and Iron Household Protein Contents in Perineuronal Net-Ensheathed Neurons Ensure Energy Metabolism with Safe Iron Handling modified: 2022-02-09T02:30:13Z cp:subject: 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. pdf:docinfo:subject: 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. 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