β-amyloid (1-42)-induced learning and memory deficits in mice:: involvement of oxidative burdens in the hippocampus and cerebral cortex
β-amyloid (1-42)-induced learning and memory deficits in mice:: involvement of oxidative burdens in the hippocampus and cerebral cortex
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DOI：
10.1016/j.bbr.2004.04.012
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发表时间：
2004-12-06
影响因子：
2.7
通讯作者：
Woo, JI
中科院分区：
文献类型：
--
作者：
Jhoo, JH;Kim, HC;Woo, JI
我们已经证明，氧化应激至少部分参与β-淀粉样蛋白（Ap）诱导的体内神经毒性[Eur.神经科学杂志1999;11：83-90; Neuroscience 2003;119：399-419]。然而，氧化应激和记忆丧失之间的机制联系，在响应Abeta仍然难以捉摸。在本研究中，我们研究了氧化应激是否有助于脑室内注射Abeta（1-42）诱导的小鼠记忆障碍。通过水迷宫和被动回避测试测量，观察到Abeta（1-42）诱导的记忆损伤，尽管在Abeta（40-1）处理的小鼠中未发现这些损伤。用抗氧化剂α-生育酚处理显著预防了由Abeta（1-42）诱导的记忆损伤。与Abeta（40-1）处理的小鼠相比，Abeta（1-42）处理的动物的海马和大脑皮层中观察到胞质Cu，Zn-SOD和线粒体Mn-SOD的活性增加。Abeta（1-42）对Cu，Zn-SOD的诱导作用明显强于Mn-SOD。然而，在用Abeta（1-42）处理的动物中未观察到响应于SOD活性显著增加的谷胱甘肽过氧化物酶（GPX）的伴随诱导。此外，谷胱甘肽还原酶（GRX）活性仅在注射Abeta（1-42）后2小时增加。在Abeta（1-42）后10天，丙二醛（脂质过氧化）和蛋白质羰基（蛋白质氧化）的产生仍然升高，但抗氧化剂α-生育酚显着防止这些氧化应激。因此，我们的研究结果表明，氧化应激有助于Abeta（1-42）诱导的小鼠学习和记忆障碍。(C)2004 Elsevier B. V.保留所有权利。
We have demonstrated that oxidative stress is involved, at least in part, in beta-amyloid protein (Ap)-induced neurotoxicity in vivo [Eur. J. Neurosci. 1999;11:83-90; Neuroscience 2003;119:399-419]. However, mechanistic links between oxidative stress and memory loss in response to Abeta remain elusive. In the present study, we examined whether oxidative stress contributes to the memory deficits induced by intracerebroventricular injection of Abeta (1-42) in mice. Abeta (1-42)-induced memory impairments were observed, as measured by the water maze and passive avoidance tests, although these impairments were not found in Abeta (40-1)-treated mice. Treatment with antioxidant alpha-tocopherol significantly prevented memory impairment induced by Abeta (1-42). Increased activities of the cytosolic Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and mitochondrial Mn-superoxide dismutase (Mn-SOD) were observed in the hippocampus and cerebral cortex of Abeta (1-42)-treated animals, as compared with Abeta (40-1)-treated mice. The induction of Cu,Zn-SOD was more pronounced than that of Mn-SOD after Abeta (1-42) insult. However, the concomitant induction of glutathione peroxidase (GPX) in response to significant increases in SOD activity was not seen in animals treated with Abeta (1-42). Furthermore, glutathione reductase (GRX) activity was only increased at 2 h after Abeta (1-42) injection. Production of malondialdehyde (lipid peroxidation) and protein carbonyl (protein oxidation) remained elevated at 10 days post-Abeta (1-42), but the antioxidant alpha-tocopherol significantly prevented these oxidative stresses. Therefore, our results suggest that the oxidative stress contributes to the Abeta (1-42)-induced learning and memory deficits in mice. (C) 2004 Elsevier B.V. All rights reserved.