Role of antioxidant enzymes in redox regulation of N-methyl-D-aspartate receptor function and memory in middle-aged rats.
Role of antioxidant enzymes in redox regulation of N-methyl-D-aspartate receptor function and memory in middle-aged rats.
复制标题
DOI：
10.1016/j.neurobiolaging.2013.12.002
复制
发表时间：
2014-06
影响因子：
4.2
通讯作者：
Foster TC
中科院分区：
文献类型：
--
作者：
Lee WH;Kumar A;Rani A;Foster TC
超氧化物歧化酶1（SOD 1）在海马中的过度表达导致年龄依赖性认知功能受损和突触可塑性改变，这表明一个可能的模型，用于检查氧化应激在衰老神经生理学中的作用。然而，目前尚不清楚，如果SOD 1过度表达涉及改变氧化还原环境和N-甲基-D-天冬氨酸受体（NMDAR）突触功能的老化动物报告的减少。使用病毒载体在中年（17月龄）雄性Fischer 344大鼠海马中表达SOD 1和绿色荧光蛋白（SOD 1 +GFP）、SOD 1和过氧化氢酶（SOD 1 +CAT）或单独表达GFP。我们证实，SOD 1 +GFP和SOD 1 +CAT减少脂质过氧化反应，表明超氧化物代谢物是主要负责脂质过氧化反应。SOD 1 +GFP损害学习，降低谷胱甘肽过氧化物酶（GPx）活性，降低谷胱甘肽（GSH）水平，降低NMDAR介导的突触反应，并损害长时程增强（LTP）。SOD 1 +CAT的共表达挽救了SOD 1表达对学习、氧化还原措施和突触功能的影响，表明该影响是由过量的过氧化氢介导的。应用还原剂二硫苏糖醇（DTT）的海马切片增加了NMDAR介导的组件的突触反应在SOD 1 +GFP动物相对于动物，过表达SOD 1 +CAT的NMDAR功能的抗氧化酶表达的影响是由于在氧化还原环境的转变。结果表明，在中年神经元SOD 1和CAT的过度表达可能提供了一个模型，用于检查氧化应激在衰老生理学和年龄相关的神经退行性疾病的进展中的作用。
Overexpression of superoxide dismutase 1 (SOD1) in the hippocampus results in age-dependent impaired cognition and altered synaptic plasticity suggesting a possible model for examining the role of oxidative stress in senescent neurophysiology. However, it is unclear if SOD1 overexpression involves an altered redox environment and a decrease in N-methyl-D-aspartate receptor (NMDAR) synaptic function reported for aging animals. Viral vectors were used to express SOD1 and green fluorescent protein (SOD1+GFP), SOD1 and catalase (SOD1+CAT), or GFP alone in the hippocampus of middle-age (17 mo) male Fischer 344 rats. We confirm that SOD1+GFP and SOD1+CAT reduced lipid peroxidation indicating superoxide metabolites were primarily responsible for lipid peroxidation. SOD1+GFP impaired learning, decreased glutathione peroxidase (GPx) activity, decreased glutathione (GSH) levels, decreased NMDAR-mediated synaptic responses, and impaired long-term potentiation (LTP). Co-expression of SOD1+CAT rescued the effects of SOD1 expression on learning, redox measures, and synaptic function suggesting the effects were mediated by excess hydrogen peroxide. Application of the reducing agent dithiolthreitol (DTT) to hippocampal slices increased the NMDAR-mediated component of the synaptic response in SOD1+GFP animals relative to animals that overexpress SOD1+CAT indicating that the effect of antioxidant enzyme expression on NMDAR function was due to a shift in the redox environment. The results suggest that overexpression of neuronal SOD1 and CAT in middle-age may provide a model for examining the role of oxidative stress in senescent physiology and the progression of age-related neurodegenerative diseases.
登录
查看更多内容
DOI：
10.1073/pnas.93.16.8530
发表时间：
1996-08-06
影响因子：
11.1
作者：
BarPeled, O;Korkotian, E;Groner, Y
通讯作者：
Groner, Y
影响因子：
4.2
作者：
FAVILLI, F;IANTOMASI, T;VINCENZINI, MT
通讯作者：
VINCENZINI, MT
影响因子：
3.6
作者：
Belrose JC;Xie YF;Gierszewski LJ;MacDonald JF;Jackson MF
通讯作者：
Jackson MF
影响因子：
--
作者：
Crivello, Natalia A.;Rosenberg, Irwin H.;Joseph, James A.
通讯作者：
Joseph, James A.
影响因子：
5.6
作者：
Brewer, Gregory J.;Torricelli, John R.;Lindsey, Amanda L.;Kunz, Elizabeth Z.;Neuman, A.;Fisher, Derek R.;Joseph, James A.
通讯作者：
Joseph, James A.