Oestreicher E, Sengstock G J, Riederer P, Olanow C W, Dunn A J, Arendash G W
Department of Psychiatry, University of Wurzburg, Germany.
Brain Res. 1994 Oct 10;660(1):8-18. doi: 10.1016/0006-8993(94)90833-8.
Parkinson's-diseased (PD) brains have increased levels of iron in the zona compacta of the substantia nigra (SNc). To determine whether these elevated nigral iron levels may be caused secondarily by degeneration of nigrostriatal dopaminergic (NS-DA) neurons, the NS-DA pathway was unilaterally lesioned in rats through 6-hydroxydopamine (6-OHDA) infusion and nigral iron levels evaluated three weeks later. A significant increase was observed in both iron concentration (+35%) and iron content (+33) within the substantia nigra (SN) ipsilateral to comprehensive 6-OHDA lesions. Moreover, ferric iron staining was dramatically increased within the SNc following 6-OHDA lesions, primarily due to the appearance of iron-positive SNc neurons and infiltrating reactive glial cells. Iron staining in the SN zona reticularis was modestly increased after 6-OHDA lesions, but staining in the neostriatum and globus pallidus was unaffected. These results indicate that loss of NS-DA neurons is associated with increased iron levels in the SN. This suggests that increased nigral iron levels in PD may be secondary to some neurodegenerative process. Nonetheless, even a secondary increase in nigral iron levels may be of pathogenic importance in PD because of iron's ability to catalyze neurotoxic free radical formation and perpetuate neurodegeneration.
帕金森病（PD）患者的大脑中，黑质致密部（SNc）的铁含量增加。为了确定黑质中铁含量升高是否可能继发于黑质纹状体多巴胺能（NS-DA）神经元的变性，通过向大鼠单侧注射6-羟基多巴胺（6-OHDA）损伤NS-DA通路，并在三周后评估黑质铁含量。在接受全面6-OHDA损伤同侧的黑质（SN）中，铁浓度（+35%）和铁含量（+33）均显著增加。此外，6-OHDA损伤后，SNc内的三价铁染色显著增加，主要是由于出现了铁阳性的SNc神经元和浸润的反应性胶质细胞。6-OHDA损伤后，SN网状带的铁染色略有增加，但新纹状体和苍白球的染色未受影响。这些结果表明，NS-DA神经元的丧失与SN中铁含量增加有关。这表明PD患者黑质中铁含量升高可能继发于某些神经退行性过程。尽管如此，即使黑质中铁含量的继发性增加在PD中也可能具有致病重要性，因为铁能够催化神经毒性自由基的形成并使神经退行性变持续下去。
