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首页> 外文学位 >Effect of ascorbic acid on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced toxicity in the brain of Balb/C mouse.
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Effect of ascorbic acid on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced toxicity in the brain of Balb/C mouse.

机译：抗坏血酸对Balb / C小鼠脑中1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的毒性的影响。

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摘要

Parkinson's disease (PD), one of the major neurodegenerative diseases, is characterized by degeneration of dopaminergic (DAergic) neurons in the nigrostriatal pathway. Among the various treatments, levodopa (L-dopa) is the one of the most common therapeutic drugs used, however, it only alleviates certain symptoms and it cannot cure the disorder due to its degenerative nature and the uncertain causes of the disease. Animal models, therefore, were developed to investigate the mechanism of PD in order to obtain better and more effective treatments for the disease.; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the common toxin-induced models of PD used in the investigation on the neuropathology of the disease. During the metabolism of MPTP, various reactive oxidative species (ROS), including superoxide radical and hydrogen peroxide, are produced, and these are believed to cause neuron degeneration. Moreover, its free radical metabolite 1-methyl-4-phenylpyridinium (MPP+), generated in astrocytes, is taken up into DAergic neurons clustered in the substantia nigra (SN) and striatum (ST), and its accumulation leads to neurodegeneration in the nigrostriatal pathway.; In this study, Balb/C mice were used to investigate the protective mechanism of ascorbic acid (AA), a well established antioxidant, against MPTP-induced toxicity in the SN and ST, the most affected brain areas in PD. As antioxidant enzymes are responsible for the removal of ROS, we examined the effect of MPTP on the antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSX), in the SN and ST. As expected, the antioxidant enzymes were induced by MPTP treatment, most likely a physiological response to scavenge the free radicals generated from MPTP, and the induction in the SN was higher than that in the ST. Prolonged AA pretreatment partly reduced the MPTP induction effect, and this may be due to antioxidative effect of AA in scavenging free radicals.; Other than superoxide radical and hydrogen peroxide, MPP+ is another ROS produced from MPTP. In order to investigate the protective effect of antioxidant on MPTP-induced oxidation, AA was administered into MPTP-treated mice and its effect on the generation and metabolism of MPP + was investigated. Following the treatment with AA (100 mg/kg body weight) for 7 days, the levels of AA were both increased in the SN and ST, suggesting that dietary AA can alter the level of AA in the brain. This increment in AA level correlated well with the increased expression of the AA transporter, sodium-dependent vitamin C transporter 2 (SVCT2), but not with glucose transporters (GLUT) 1 and 3, that are responsible for dehydroascorbic acid transport. In addition, AA pretreatment apparently lowered the conversion of MPTP to MPP+ in both brain areas in which the reduction in the ST was higher than in the SN. We postulated that this reduction in MPP+ was due to the scavenging effect of AA, and this was supported by the finding that AA reduced the production of MPP+ in cultured astrocytes. (Abstract shortened by UMI.)
机译：帕金森氏病（PD）是主要的神经退行性疾病之一，其特征是黑质纹状体途径中的多巴胺能（DAergic）神经元变性。在各种治疗方法中，左旋多巴（L-多巴）是最常用的治疗药物之一，但是，由于其退行性和不确定的疾病原因，它只能缓解某些症状并且不能治愈该疾病。因此，建立了动物模型以研究PD的机制，以便获得对该病更好更好的治疗方法。 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）是一种常见的毒素诱导的PD模型，用于研究该疾病的神经病理学。在MPTP的代谢过程中，会产生各种反应性氧化物质（ROS），包括超氧自由基和过氧化氢，并且据信它们会引起神经元变性。此外，其在星形胶质细胞中产生的自由基代谢物1-甲基-4-苯基吡啶鎓（MPP +）被聚集在黑质（SN）和纹状体（ST）中的DA能神经元中，其积累导致黑质纹状体中的神经变性。途径。在这项研究中，Balb / C小鼠用于研究抗坏血酸（AA）（一种完善的抗氧化剂）针对MPTP诱导的SN和ST（PD受累最严重的大脑区域）中的毒性的保护机制。由于抗氧化酶负责去除ROS，因此我们研究了MPTP对SN和ST中抗氧化酶，超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSX）的影响。不出所料，抗氧化剂酶是通过MPTP处理诱导的，很可能是生理反应以清除MPTP产生的自由基，并且在SN中的诱导高于在ST中。长时间的AA预处理会部分降低MPTP的诱导作用，这可能是由于AA在清除自由基方面的抗氧化作用。除了超氧自由基和过氧化氢，MPP +是MPTP产生的另一种ROS。为了研究抗氧化剂对MPTP诱导的氧化的保护作用，将AA给予MPTP处理的小鼠，并研究其对MPP +生成和代谢的影响。用AA（100 mg / kg体重）治疗7天后，SN和ST中的AA水平均升高，这表明饮食AA可以改变大脑中AA的水平。 AA水平的这种增加与AA转运蛋白，钠依赖性维生素C转运蛋白2（SVCT2）的表达增加高度相关，但与负责脱氢抗坏血酸转运的葡萄糖转运蛋白（GLUT）1和3却没有相关性。此外，AA预处理明显降低了两个脑区的MPTP向MPP +的转化，其中ST的降低高于SN。我们推测MPP +的减少是由于AA的清除作用所致，这一发现得到了AA减少培养的星形胶质细胞MPP +产生的支持。 （摘要由UMI缩短。）

著录项

  • 作者

    Chan, Tak Yee Bonita.;

  • 作者单位

    The Chinese University of Hong Kong (People's Republic of China).;

  • 授予单位 The Chinese University of Hong Kong (People's Republic of China).;
  • 学科 Biology Neuroscience.; Health Sciences Nutrition.
  • 学位 Ph.D.
  • 年度 2004
  • 页码 137 p.
  • 总页数 137
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经科学;预防医学、卫生学;
  • 关键词

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