Molecular manipulations of extracellular superoxide dismutase: Functional importance for learning
Molecular manipulations of extracellular superoxide dismutase: Functional importance for learning
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DOI：
10.1023/a:1021673703129
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发表时间：
1998-09-01
影响因子：
2.6
通讯作者：
Crapo, JD
中科院分区：
文献类型：
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作者：
Levin, ED;Brady, TC;Crapo, JD
胞外超氧化物歧化酶（EC-SOD）控制胞外超氧化物（O-2（.-））的可用性，其对于多种生理途径（包括使一氧化氮（NO）失活的主要手段）是重要的。EC-SOD在神经行为功能中的作用至今尚未被探索。在当前的研究中，小鼠EC-SOD产生的表型表达或基因型改变的特征在于空间学习和记忆。EC-SOD基因敲除小鼠和EC-SOD基因过表达小鼠在Win-shift X-arm径向迷宫中的空间学习能力均明显受损。EC-SOD过表达小鼠的进一步特征在于在径向臂迷宫中的重复获取任务中具有显著缺陷，这允许分离长期和短期学习。EC-SOD过度表达显著损害了长期学习能力，而EC-SOD过度表达对短期学习能力没有显著影响。NO系统已被证明在学习和记忆中起重要作用。这可能是重要的，在目前的研究中，因为EC-SOD的主要控制失活的NO。我们发现，EC-SOD过表达小鼠的认知L-NAME（NG-硝基-L-精氨酸甲酯盐酸盐），一氧化氮合酶抑制剂的影响。这些小鼠中NO催化剂的减少可能起到对抗L-NAME抑制NOS的作用。目前的研究发现，EC-SOD水平高于或低于对照组损害学习表明，适当控制脑细胞外O-2（.-）可能比仅仅减少脑细胞外O-2（.-）保持足够的学习功能。
Extracellular superoxide dismutase (EC-SOD) controls the availability of extracellular superoxide (O-2(.-)), which is important for a variety of physiological pathways, including the primary means of inactivating nitric oxide (NO). The role of EC-SOD in neurobehavioral function has been until now unexplored. in the current studies, the phenotypic expression of genotypic alterations of EC-SOD production in mice were characterized for spatial learning and memory. Dramatic impairments in spatial learning in the win-shift X-arm radial maze were seen in both EC-SOD knockout mice and EC-SOD overexpressing mice. The EC-SOD overexpressing mice were further characterized as having significant deficits in a repeated acquisition task in the radial-arm maze, which permitted the dissociation of long and short-term learning. Long-term learning was significantly impaired by EC-SOD overexpression, whereas short-term learning was not significantly affected by EC-SOD overexpression. NO systems have been shown to be importantly involved in learning and memory. This may be important in the current studies because EC-SOD has primary control over the inactivation of NO. We found that EC-SOD overexpressing mice were resistant to the cognitive effects of L-NAME (NG-nitro-L-arginine methyl ester hydrochloride), an NO synthase inhibitor. Decreased NO catabolism in these mice may have served to counter the effects of NOS inhibition by L-NAME. The current finding that EC-SOD levels that were either higher or lower than controls impaired learning demonstrates that the proper control of brain extracellular O-2(.-) may be more vital than merely reduction of brain extracelluar O-2(.-) in maintaining adequate learning function.