Selective neuronal vulnerability and inadequate stress response in superoxide dismutase mutant mice
Selective neuronal vulnerability and inadequate stress response in superoxide dismutase mutant mice
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DOI：
10.1016/j.freeradbiomed.2004.12.020
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发表时间：
2005-03-15
影响因子：
7.4
通讯作者：
Huang, TT
中科院分区：
文献类型：
--
作者：
Lynn, S;Huang, EJ;Huang, TT
为了了解氧化应激和线粒体缺陷在神经退行性疾病发展中的作用，我们检查了线粒体超氧化物歧化酶（MnSOD，SOD2）缺陷的纯合突变小鼠中与年龄相关的病理变化和相应的基因表达谱。这些 Sod2-/- 小鼠产生 B6D2F1 背景的油，在出生后第 11 天出现共济失调，并在 P14 时随着频繁癫痫发作而逐渐恶化。组织病理学检查显示神经退行性改变与神经系统体征一致。在整个脑干和喙皮质的神经元和神经纤维中观察到空泡变性。脑干运动三叉神经核和运动皮层深层是最早退化的区域，丘脑和海马在后期受到影响。使用寡核苷酸微阵列比较 Sod2+/+ 和 -/- 小鼠从出生到 P18 的脑干和丘脑的基因表达谱。值得注意的是，大量热休克蛋白基因转录下调，这很可能是由于热休克转录因子 I (HSF1) 的减少所致。其他主要类别的差异表达基因包括脂质生物合成和活性氧代谢。 (C) 2004 Elsevier Inc. 保留所有权利。
To understand the role of oxidative stress and mitochondrial defects in the development of neurodegeneration, we examined the age-related pathological changes and corresponding gene expression profiles in homozygous mutant mice deficient in the mitochondrial form of superoxide dismutase (MnSOD, SOD2). These Sod2-/- mice, generated oil a B6D2F1 background, developed ataxia at Postnatal Day (P) 11 and progressively deteriorated with frequent seizures by P14. Histopathological examination revealed neurodegenerative changes Consistent With the neurological signs. Vacuolar degeneration was observed in neurons and neuropil throughout the brainstem and rostral cortex. The motor trigeminal nucleus in brainstem and the deeper layers of the motor cortex were the earliest regions to degenerate, with the thalamus and hippocampus affected at later stages. Oligonucleotide microarrays were used to compare gene expression profiles in the brainstem and thalamus of Sod2+/+ and -/- mice from birth to P18. Notably, a large set of heat-shock protein genes was transcriptionally down regulated, and this was most likely due to a reduction in the heat-shock transcription factor I (HSF1). Other major classes of differentially expressed genes include lipid biosynthesis and ROS metabolism. (C) 2004 Elsevier Inc. All rights reserved.