Oxidative stress and neuronal DNA fragmentation mediate age-dependent vulnerability to the mitochondrial toxin, 3-nitropropionic acid, in the mouse striatum

Oxidative stress and neuronal DNA fragmentation mediate age-dependent vulnerability to the mitochondrial toxin, 3-nitropropionic acid, in the mouse striatum
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DOI:
10.1006/nbdi.2000.0327
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发表时间:
2001-02-01
影响因子:
6.1
通讯作者:
Chan, PH
Chan, PH
中科院分区:
医学1区
文献类型:
--
作者:
Kim, GW;Chan, PH

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氧化应激参与了多种神经退行性疾病和中风的神经病理学,所有这些都与兴奋性毒性有关。这些条件的特点是依赖于企业的脆弱性。目前尚不清楚是否阿尔茨海默病相关的神经元死亡参与年龄依赖性的脆弱性兴奋毒性。我们评估了用3-硝基丙酸(3-NP)处理后,小鼠纹状体中与癫痫相关的神经元死亡是否具有年龄依赖性。我们已经证明,3-NP治疗后早期发生氧化应激,在老年小鼠中更是如此。末端脱氧核苷酸转移酶介导的尿苷5 '-三磷酸-生物素缺口末端标记染色和凝胶电泳的DNA片段化以年龄依赖的方式发生。DNA修复酶,脱嘌呤/脱嘧啶核酸内切酶的表达,在老年小鼠中更衰减。因此,这些结果表明,氧化应激诱导3-NP处理后,在小鼠纹状体中的年龄依赖性神经元凋亡,这反过来又产生了年龄依赖性的脆弱性3-NP。(C)北京:科学出版社.
Oxidative stress is involved in the neuropathology of several neurodegenerative diseases and stroke, all of which are related to excitotoxicity. Age-dependent vulnerability is characteristic of these conditions. It is not clear whether apoptosis-related neuronal death is involved in age-dependent vulnerability to excitotoxicity. We evaluated whether apoptosis-related neuronal death after treatment with 3-nitropropionic acid (3-NP) is age-dependent in the mouse striatum. We have demonstrated that oxidative stress occurs early after 3-NP treatment and even more so in aged mice. DNA fragmentation with terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling staining and gel electrophoresis occurred in an age-dependent fashion. Expression of the DNA repair enzyme, apurinic/apyrimidinic endonuclease, was more attenuated in old mice. Therefore, these results suggest that oxidative stress induces age-dependent neuronal apoptosis in the mouse striatum after 3-NP treatment, which in turn produces an age-dependent vulnerability to 3-NP. (C) 2001 Academic Press.