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首页> 外文学位 >Viral transfection of mesenchymal stem cells to overexpress brain-derived neurotrophic factor and nerve growth factor as potential therapies for reducing behavioral deficits in the YAC 128 mouse model of Huntington's disease.
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Viral transfection of mesenchymal stem cells to overexpress brain-derived neurotrophic factor and nerve growth factor as potential therapies for reducing behavioral deficits in the YAC 128 mouse model of Huntington's disease.

机译：间充质干细胞的病毒转染以过度表达脑源性神经营养因子和神经生长因子，作为减少亨廷顿氏病YAC 128小鼠模型行为缺陷的潜在疗法。

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摘要

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and emotional dysfunction. HD is caused by polyglutamine expansion in the IT15 region of chromosome 4 leading to selective degeneration of the medium sized spiny neurons (MSSN) of the striatum. Instrastriatal infusions of trophic factors, such as brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF), have been shown to attenuate deficits in HD animal models, but this method of delivery only allows for short-term delivery of trophic factors. Cellular delivery of these factors has been shown to lead to a reduction in behavioral deficits but graft rejection often occurs due the body's immune response.;The current study evaluated the use of mesenchymal stem cells (MSC), which are known to be hypo-immunogenic, as a means of trophic factor delivery with a lower risk of immune rejection. MSCs, harvested from mouse femurs, were virally transfected to overexpress either brain derived neurotrophic factor (BDNF) or nerve growth factor (NGF). These cells or a vehicle solution were transplanted into the striata of YAC 128 transgenic HD mice and littermate controls at 4 months and behavioral testing was carried out in order to determine the motor and cognitive effects of transplantation. Mice were sacrificed at 13 months for immunohistological examination.;YAC 128 mice that received virally transfected MSCs showed an attenuation of cognitive and motor deficits. YAC 128 mice that received MSCs virally transfected to overexpress BDNF tended to show the greatest amount of behavioral recovery in motor tasks whereas mice that received MSCs virally transfected to overexpress NGF performed better in cognitive tasks. Histological analysis revealed that YAC 128 mice that received BDNF transfected MSCs had sparing of MSSNs and larger striata compared to untreated YAC 128 mice.;These results indicate that the use of virally-transfected MSCs may create an environment within the striatum that potentially abates or slows the dysfunction and neurodegeneration observed in the YAC 128 mouse model of HD. Further research on the long-term safety and efficacy of this approach is needed before its potential clinical utility can be assessed.
机译：亨廷顿舞蹈病（HD）是一种神经退行性疾病，其特征在于运动，认知和情感功能障碍。 HD是由4号染色体IT15区域中的聚谷氨酰胺膨胀引起的，从而导致纹状体的中型多刺神经元（MSSN）选择性变性。已经证明在营养体的基础上输注脑源性神经营养因子（BDNF）和神经生长因子（NGF）等营养因子可减轻HD动物模型中的缺陷，但是这种递送方法仅允许短期递送营养因子。这些因素的细胞传递已被证明可以减少行为缺陷，但移植物排斥通常是由于人体的免疫反应而发生的。本研究评估了间充质干细胞（MSC）的使用，该细胞具有低免疫原性，作为传递营养因子的方法，具有较低的免疫排斥风险。将从小鼠股骨中收获的MSC进行病毒转染以过表达脑源性神经营养因子（BDNF）或神经生长因子（NGF）。这些细胞或媒介物溶液在4个月时被移植到YAC 128转基因HD小鼠的横纹和同窝对照中，并进行了行为测试以确定移植的运动和认知作用。在13个月时处死小鼠以进行免疫组织学检查。接受病毒转染的MSC的YAC 128小鼠表现出认知和运动缺陷的减弱。接受病毒转染过表达BDNF的MSC的YAC 128小鼠在运动任务中表现出最大的行为恢复，而接受病毒转染过表达NGF的MSC的小鼠在认知任务中表现更好。组织学分析表明，与未经治疗的YAC 128小鼠相比，接受BDNF转染的MSC的YAC 128小鼠具有MSSN和较细的纹状体稀疏;这些结果表明，使用病毒转染的MSC可能会在纹状体内创造一个可能减弱或减慢的环境在HD的YAC 128小鼠模型中观察到的功能障碍和神经退行性变。在评估该方法的潜在临床实用性之前，需要对该方法的长期安全性和有效性进行进一步研究。

著录项

  • 作者

    Dey, Nicholas D.;

  • 作者单位

    Central Michigan University.;

  • 授予单位 Central Michigan University.;
  • 学科 Biology Neuroscience.;Psychology Psychobiology.;Psychology Experimental.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 117 p.
  • 总页数 117
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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