Subthalamic hGAD65 Gene Therapy and Striatum TH Gene Transfer in a Parkinson’s Disease Rat Model
The aim of the present study is to detect a combination method to utilize gene therapy for the treatment of Parkinson’s disease (PD). Here, a PD rat model is used for the in vivo gene therapy of a recombinant adeno-associated virus (AAV2) containing a human glutamic acid decarboxylase 65 (rAAV2-hGAD...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2013/263287 |
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| author | Deyu Zheng Xiaohua Jiang Junpeng Zhao Deyi Duan Huanying Zhao Qunyuan Xu |
| author_facet | Deyu Zheng Xiaohua Jiang Junpeng Zhao Deyi Duan Huanying Zhao Qunyuan Xu |
| author_sort | Deyu Zheng |
| collection | DOAJ |
| description | The aim of the present study is to detect a combination method to utilize gene therapy for the treatment of Parkinson’s disease (PD). Here, a PD rat model is used for the in vivo gene therapy of a recombinant adeno-associated virus (AAV2) containing a human glutamic acid decarboxylase 65 (rAAV2-hGAD65) gene delivered to the subthalamic nucleus (STN). This is combined with the ex vivo gene delivery of tyrosine hydroxylase (TH) by fibroblasts injected into the striatum. After the treatment, the rotation behavior was improved with the greatest efficacy in the combination group. The results of immunohistochemistry showed that hGAD65 gene delivery by AAV2 successfully led to phenotypic changes of neurons in STN. And the levels of glutamic acid and GABA in the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr) were obviously lower than the control groups. However, hGAD65 gene transfer did not effectively protect surviving dopaminergic neurons in the SNc and VTA. This study suggests that subthalamic hGAD65 gene therapy and combined with TH gene therapy can alleviate symptoms of the PD model rats, independent of the protection the DA neurons from death. |
| format | Article |
| id | doaj-art-c6a8417d43614f56bba0f45eddf63912 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-c6a8417d43614f56bba0f45eddf639122025-02-03T06:11:02ZengWileyNeural Plasticity2090-59041687-54432013-01-01201310.1155/2013/263287263287Subthalamic hGAD65 Gene Therapy and Striatum TH Gene Transfer in a Parkinson’s Disease Rat ModelDeyu Zheng0Xiaohua Jiang1Junpeng Zhao2Deyi Duan3Huanying Zhao4Qunyuan Xu5Beijing Institute for Neuroscience, Beijing Center for Neural Regeneration & Repair, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Capital Medical University, Beijing 100069, ChinaBeijing Institute for Neuroscience, Beijing Center for Neural Regeneration & Repair, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Capital Medical University, Beijing 100069, ChinaBeijing Institute for Neuroscience, Beijing Center for Neural Regeneration & Repair, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Capital Medical University, Beijing 100069, ChinaBeijing Institute for Neuroscience, Beijing Center for Neural Regeneration & Repair, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Capital Medical University, Beijing 100069, ChinaBeijing Institute for Neuroscience, Beijing Center for Neural Regeneration & Repair, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Capital Medical University, Beijing 100069, ChinaBeijing Institute for Neuroscience, Beijing Center for Neural Regeneration & Repair, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Capital Medical University, Beijing 100069, ChinaThe aim of the present study is to detect a combination method to utilize gene therapy for the treatment of Parkinson’s disease (PD). Here, a PD rat model is used for the in vivo gene therapy of a recombinant adeno-associated virus (AAV2) containing a human glutamic acid decarboxylase 65 (rAAV2-hGAD65) gene delivered to the subthalamic nucleus (STN). This is combined with the ex vivo gene delivery of tyrosine hydroxylase (TH) by fibroblasts injected into the striatum. After the treatment, the rotation behavior was improved with the greatest efficacy in the combination group. The results of immunohistochemistry showed that hGAD65 gene delivery by AAV2 successfully led to phenotypic changes of neurons in STN. And the levels of glutamic acid and GABA in the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr) were obviously lower than the control groups. However, hGAD65 gene transfer did not effectively protect surviving dopaminergic neurons in the SNc and VTA. This study suggests that subthalamic hGAD65 gene therapy and combined with TH gene therapy can alleviate symptoms of the PD model rats, independent of the protection the DA neurons from death.http://dx.doi.org/10.1155/2013/263287 |
| spellingShingle | Deyu Zheng Xiaohua Jiang Junpeng Zhao Deyi Duan Huanying Zhao Qunyuan Xu Subthalamic hGAD65 Gene Therapy and Striatum TH Gene Transfer in a Parkinson’s Disease Rat Model Neural Plasticity |
| title | Subthalamic hGAD65 Gene Therapy and Striatum TH Gene Transfer in a Parkinson’s Disease Rat Model |
| title_full | Subthalamic hGAD65 Gene Therapy and Striatum TH Gene Transfer in a Parkinson’s Disease Rat Model |
| title_fullStr | Subthalamic hGAD65 Gene Therapy and Striatum TH Gene Transfer in a Parkinson’s Disease Rat Model |
| title_full_unstemmed | Subthalamic hGAD65 Gene Therapy and Striatum TH Gene Transfer in a Parkinson’s Disease Rat Model |
| title_short | Subthalamic hGAD65 Gene Therapy and Striatum TH Gene Transfer in a Parkinson’s Disease Rat Model |
| title_sort | subthalamic hgad65 gene therapy and striatum th gene transfer in a parkinson s disease rat model |
| url | http://dx.doi.org/10.1155/2013/263287 |
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