Gahtan E, Auerbach J M, Groner Y, Segal M
Department of Neurobiology, The Weizmann Institute, Rehovot, Israel.
Eur J Neurosci. 1998 Feb;10(2):538-44. doi: 10.1046/j.1460-9568.1998.00058.x.
Copper/zinc superoxide dismutase (CuZn-SOD) is a key enzyme in the metabolism of oxygen free radicals. The gene encoding CuZn-SOD resides on human chromosome 21 and is overexpressed in Down syndrome (DS) patients. Overexpression of CuZn-SOD in transgenic (Tg) mice and cultured cells creates chronic oxidative stress leading to enhanced susceptibility to degeneration and apoptotic cell death. We have now found that three lines of Tg-CuZn-SOD mice, one of which also overexpresses S100beta, a glial calcium binding protein, are deficient in spatial memory. Furthermore, hippocampal slices taken from these mice have an apparently normal synaptic physiology, but are impaired in the ability to express long-term potentiation (LTP). This effect on hippocampal LTP was abrogated by treatment of slices with the H2O2 scavenger catalase or the antioxidant N-t-butyl-phenylnitrone (BPN). It is proposed that elevated CuZnSOD causes an increase in tetanic stimulation-evoked formation of H2O2 which leads to diminished LTP and cognitive deficits in these mice.
铜锌超氧化物歧化酶（CuZn-SOD）是氧自由基代谢中的关键酶。编码CuZn-SOD的基因位于人类21号染色体上，在唐氏综合征（DS）患者中过度表达。在转基因（Tg）小鼠和培养细胞中CuZn-SOD的过度表达会产生慢性氧化应激，导致对退化和凋亡性细胞死亡的易感性增强。我们现在发现，三系Tg-CuZn-SOD小鼠，其中一系还过度表达S100β（一种神经胶质钙结合蛋白），存在空间记忆缺陷。此外，取自这些小鼠的海马切片具有明显正常的突触生理学，但在表达长时程增强（LTP）的能力方面受损。用H2O2清除剂过氧化氢酶或抗氧化剂N-叔丁基苯硝酮（BPN）处理切片可消除这种对海马LTP的影响。有人提出，升高的CuZnSOD会导致强直刺激诱发的H2O2形成增加，从而导致这些小鼠的LTP减弱和认知缺陷。
