Institute of Anatomy, Histology and Embryology, Leipzig University, An den Tierkliniken 43, 04103 Leipzig, Germany.
Paul Flechsig Institute of Brain Research, Leipzig University, Liebigstraße 19, 04103 Leipzig, Germany.
Int J Mol Sci. 2022 Jan 31;23(3):1634. doi: 10.3390/ijms23031634.
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 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.
神经元亚群对铁诱导的氧化应激和神经退行性变的脆弱性较低。这些神经元的一个关键特征是特殊的细胞外基质组成，形成了周围神经鞘（PN）。PN 对铁具有高亲和力，这表明被鞘包裹的神经元具有适应性的铁隔离和代谢。高度活跃、快速放电的神经元——通常被 PN 包裹——具有特殊的高代谢需求，因此可能对铁的需求更高。我们假设 PN 包裹的神经元具有更高的细胞内铁浓度和增加的铁蛋白水平。因此，我们对顶叶皮层（PC）、下托（SUB）、红核（RN）和黑质（SNpr/SNpc）中的大鼠进行了细胞和区域铁以及铁蛋白转铁蛋白（Tf）、Tf 受体 1（TfR）、铁蛋白 H/L（FtH/FtL）、金属转运蛋白 1（MTP1，又名亚铁蛋白）和二价金属转运蛋白 1（DMT1）的分析。具有 PN 的神经元的铁浓度高于没有 PN 的神经元：PC 为 0.69 mM 对 0.51 mM，SUB 为 0.84 mM 对 0.69 mM，SN 为 0.71 mM 对 0.63 mM（SNpr）/0.45 mM（SNpc）。PN 神经元的细胞内 Tf、TfR 和 MTP1 含量均增加。PN 本身的铁浓度没有增加。我们还确定了 PN 神经元的百分比：PC 为 4%，SUB 为 5%，SNpr 为 45%，RN 为 86%。我们的结论是，PN 神经元构成了具有活跃铁代谢和出色铁处理能力的抗应激神经元亚群。这些特性可能有助于 PN 神经元抵抗铁诱导的氧化应激和变性的脆弱性。
