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Long-term restoration of nigrostriatal system function by implanting GDNF genetically modified fibroblasts in a rat model of Parkinson’s disease

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Abstract

The motor behavior and levels of dopamine and its metabolites in the striatum were studied in rats that received a unilateral injection of 6-OHDA and underwent grafting of rat-derived primary fibroblasts that had been genetically modified to express lacZ and human glial cell line-derived neurotrophic factor (GDNF). Rotation behavior tests were performed each week and striatal levels of DA and its metabolites were measured every 4 weeks after grafting of fibroblasts that expressed lacZ, with or without additional transfection of the GDNF transgene. Rats grafted with GDNF-producing fibroblasts showed a significant improvement in motor behavior as determined by the rotation test, with a less pronounced reduction in the levels of dopamine and its metabolites in the striatum as compared with those in the control animals or brain parts. In addition, there was a lower decrease in the number of TH immunoreactive neurons in the substantia nigra ipsilateral to the lesion in rats with GDNF-producing fibroblasts than in rats with lacZ-expressing fibroblasts. These results support the notion that intracerebral grafting of fibroblasts that express GDNF is a potentially useful therapeutic strategy for treating Parkinson’s disease.

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Acknowledgements

This study was partly supported by the National Natural Science Foundation of China (contract no. 39780037), National Key Technologies R&D Program of China (contract no. 96-901-06-51), and Beijing Municipal Education Commission, China (contract no. 00KJ105).

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Authors and Affiliations

  1. Beijing Institute for Neuroscience and Beijing Center for Neural Regeneration and Repairing, Capital University of Medical Sciences, 100054, Beijing, China

    Deyi Duan, Hui Yang, Jingzhong Zhang, Jingzhong Zhang, Jinlu Zhang, Jinlu Zhang & Qunyuan Xu

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  1. Deyi Duan
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  2. Hui Yang
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  3. Jingzhong Zhang
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  4. Jinlu Zhang
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  5. Qunyuan Xu
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Correspondence to Qunyuan Xu.

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Duan, D., Yang, H., Zhang, J. et al. Long-term restoration of nigrostriatal system function by implanting GDNF genetically modified fibroblasts in a rat model of Parkinson’s disease. Exp Brain Res 161, 316–324 (2005). https://doi.org/10.1007/s00221-004-2075-y

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  • DOI: https://doi.org/10.1007/s00221-004-2075-y

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