Oxidative stress is associated with region-specific neuronal death during thiamine deficiency
Oxidative stress is associated with region-specific neuronal death during thiamine deficiency
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DOI：
10.1097/00005072-199909000-00005
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发表时间：
1999-09-01
影响因子：
3.2
通讯作者：
Gibson, GE
中科院分区：
文献类型：
--
作者：
Calingasan, NY;Chun, WJ;Gibson, GE
硫胺素缺乏（TD）是氧化代谢慢性受损和选择性神经元丢失的一个模型。TD导致小鼠大脑中特定区域的神经元死亡以及巨噬细胞/小胶质细胞中诱导型一氧化氮合酶（iNOS）升高。丘脑下内侧核中神经元死亡初始部位的确定使我们能够检验iNOS和氧化应激在TD诱导的神经元死亡中的作用。TD 9天后开始出现的神经元丢失模式与小胶质细胞中氧化应激标志物血红素加氧酶 - 1（HO - 1）的诱导重叠。TD 11天后，神经元死亡和小胶质细胞HO - 1诱导扩散至整个丘脑。与以往研究一样，从第10天开始，活性铁和铁蛋白在小胶质细胞中积累。脂质过氧化产物4 - 羟基壬烯醛（HNE）仅在TD 11天后在剩余的丘脑神经元中积累。这些反应不太可能由iNOS介导，因为在iNOS基因敲除小鼠和野生型对照中HO - 1诱导和HNE积累相当。这些结果表明，在TD期间，区域和细胞特异性氧化应激与选择性神经变性相关。因此，TD是一个有用的模型，有助于阐明在与氧化应激相关的神经退行性疾病中神经元 - 小胶质细胞的相互作用。
Thiamine deficiency (TD) is a model of chronic impairment of oxidative metabolism and selective neuronal loss. TD leads to region-specific neuronal death and elevation of inducible nitric oxide synthase (iNOS) in macrophages/microglia in mouse brain. Identification of the initial site of neuronal death in the submedial thalamic nucleus allowed us to test the role of iNOS and oxidative stress in TD-induced neuronal death. The pattern of neuronal loss, which begins after 9 days of TD, overlapped with induction of the oxidative stress marker heme oxygenase-1 (HO-1) in microglia. Neuronal death and microglial HO-1 induction spread to engulf the whole thalamus after II days of TD. As in past studies, reactive iron and ferritin accumulated in microglia beginning on day 10. The lipid peroxidation product, 4-hydroxynonenal (HNE) accumulated in the remaining thalamic neurons only after 11 days of TD. These responses were not likely mediated by iNOS because HO-1 induction and HNE accumulation were comparable in iNOS knockout mice and wild-type controls. These results show that region and cell specific oxidative stress is associated with selective neurodegeneration during TD. Thus, TD is a useful model to help elucidate neuron-microglial interaction in neurodegenerative diseases associated with oxidative stress.