Inflammation and age-related iron accumulation in F344 rats.
Inflammation and age-related iron accumulation in F344 rats.
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DOI：
10.2174/1874609810801020112
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发表时间：
2008-06
影响因子：
--
通讯作者：
Randy L. Hunter;Mei Liu;D. Choi;W. Cass;G. Bing
中科院分区：
文献类型：
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作者：
Randy L. Hunter;Mei Liu;D. Choi;W. Cass;G. Bing
有证据表明，慢性炎症和铁积累可能在帕金森病（PD）的发病机制中发挥作用，因为炎症和铁水平随着年龄的增长而增加，并出现在疾病病理中。据推测，随着年龄的增长，炎症反应的加重和铁的积累增加了氧化应激，参与了PD的发病机制。经颅注射细菌内毒素脂多糖（LPS）可诱导小胶质细胞活化、氧化应激、线粒体损伤、铁积累和黑质内多巴胺能神经变性。我们对纹状体注射LPS会增加老龄大鼠黑质铁积累的假设进行了验证。我们的研究结果显示，注射后4周，LPS显著增加老龄大鼠小胶质细胞活化、脂质过氧化、铁蛋白表达和总黑质铁含量。此外，LPS显著改变了同型香草酸对多巴胺的转换比率。因此，与年龄相关的铁含量增加以及对炎症的易感性可能在pd相关的神经变性中发挥重要作用，因为炎症反应产生的自由基可以通过亚铁催化芬顿化学的增加而变得更有毒性。这可能会增强氧化应激，加剧小胶质细胞的激活，并推动PD的进展。
Evidence suggests chronic inflammation and iron accumulation may play a role in the pathogenesis of Parkinson's disease (PD) as inflammation and iron levels increase with age and appear in the disease pathology. It is hypothesized that an aggravated inflammatory response and iron accumulation, as a function of age, increase oxidative stress and participate in the pathogenesis of PD. Intracranial injection of the bacterial endotoxin, lipopolysaccharide (LPS), has been shown to induce microglia activation, oxidative stress, mitochondrial impairment, iron accumulation, and dopaminergic neurodegeneration within the substantia nigra. We tested the hypothesis that injection of LPS into the striatum would increase iron accumulation in the substantia nigra of aged rats compared to young ones. Our results showed that four weeks post injection, LPS significantly increased microglia activation, lipid peroxidation, ferritin expression, and total nigral iron content in aged rats. In addition, LPS significantly altered the turnover ratio of homovanillic acid to dopamine. Thus, an age-related increase in iron as well as susceptibility to inflammation may play an important role in PD-related neurodegeneration, as free radicals produced from the inflammatory response can become more toxic through increased ferrous iron catalyzed Fenton chemistry. This may enhance oxidative stress, exacerbate microglia activation, and drive the progression of PD.