首页> 外文学位 >Immunolesioning of identified motoneuron pools by the intramuscular injection of the immunotoxins, 192-IgG-saporin and OX7-saporin, in rats.
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Immunolesioning of identified motoneuron pools by the intramuscular injection of the immunotoxins, 192-IgG-saporin and OX7-saporin, in rats.

机译:通过肌内注射免疫毒素192-IgG-saporin和OX7-saporin在大鼠中对鉴定的运动神经元库进行免疫分离。

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摘要

Many animal models have been developed to study motoneuron diseases, including amyotrophic lateral sclerosis (ALS), which involves the selective degeneration of upper and/or lower motoneurons (MNs). Unfortunately, the animal models developed, to date, have characteristics that limit their utility for assessing the therapeutic value of cell replacement strategies, including stem cells, for the treatment of MN diseases. Recently, immunotoxins have been developed which may allow for a more selective lesion of cells not previously obtained with other techniques. Immunotoxins combine the specificity of a monoclonal antibody with the cytotoxicity of a ribosome-inactivating protein.; In this study, two immunotoxins, 192-IgG-saporin and OX7-saporin, have been used to lesion motoneurons in the neonatal and adult rat respectively. Moreover, this study demonstrates for the first time that MNs in the neonatal rat can interalize the monoclonal antibody, 192-IgG conjugated to Cy3 or saporin, by receptor-mediated endocytosis. Once internalized, 192-IgG-Cy3/-saporin are retrogradely transported to the soma of MNs within the spinal cord. The novel finding that the immunotoxin, 192-IgG-saporin, can be used to lesion MNs following an intramuscular (I.M.) injection in neonatal rats has not previously been demonstrated. In addition, this study provides strong evidence that the observed muscular atrophy following an I.M. injection of 192-IgG-saporin in neonatal rats is likely due to direct necrotic effects on the muscle. Finally, this study also demonstrates that the immunotoxin, OX7-saporin, can produce MN loss following I.M. injection in adult rats, but unlike 192-IgG-saporin, does not result in severe muscular atrophy. This may serve as a useful model for studying cell replacement strategies for motoneuron diseases like ALS.
机译:已经开发出许多动物模型来研究运动神经元疾病,包括肌萎缩性侧索硬化症(ALS),其涉及上部和/或下部运动神经元(MNs)的选择性变性。不幸的是,迄今为止,开发的动物模型具有限制其用于评估细胞替代策略(包括干细胞)用于治疗MN疾病的治疗价值的实用性的特征。近来,已经开发了免疫毒素,其可以允许以前用其他技术无法获得的细胞更具选择性的病变。免疫毒素结合了单克隆抗体的特异性和核糖体失活蛋白的细胞毒性。在这项研究中,两种免疫毒素分别是192-IgG-saporin和OX7-saporin,用于新生鼠和成年鼠的运动神经元。而且,该研究首次证明新生大鼠中的MNs可以通过受体介导的胞吞作用使与Cy3或saporin结合的单克隆抗体192-IgG发生作用。内化后,192-IgG-Cy3 / -saporin逆行转运至脊髓内MN的体。先前尚未证明在肌肉内(I.M.)注射后免疫毒素192-IgG-saporin可用于病变MN的新发现。另外,这项研究提供了强有力的证据,即在新生大鼠中IM注射192-IgG-saporin后观察到的肌肉萎缩很可能是由于对肌肉的直接坏死作用所致。最后,这项研究还证明免疫毒素OX7-saporin可以在成年大鼠注射IM后产生MN丢失,但与192-IgG-saporin不同,它不会导致严重的肌肉萎缩。这可能是研究运动神经元疾病(如ALS)的细胞替代策略的有用模型。

著录项

  • 作者

    Peterson, William Earl.;

  • 作者单位

    University of Manitoba (Canada).;

  • 授予单位 University of Manitoba (Canada).;
  • 学科 Biology Animal Physiology.; Biology Neuroscience.
  • 学位 M.Sc.
  • 年度 2002
  • 页码 69 p.
  • 总页数 69
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生理学;神经科学;
  • 关键词

  • 入库时间 2022-08-17 11:46:03

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