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...

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Veröffentlicht in:Neural plasticity. - 1998. - 2013(2013) vom: 15., Seite 263287
1. Verfasser: Zheng, Deyu (VerfasserIn)
Weitere Verfasser: Jiang, Xiaohua, Zhao, Junpeng, Duan, Deyi, Zhao, Huanying, Xu, Qunyuan
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2013
Zugriff auf das übergeordnete Werk:Neural plasticity
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Oxidopamine 8HW4YBZ748 Tyrosine 3-Monooxygenase EC 1.14.16.2 Glutamate Decarboxylase EC 4.1.1.15 glutamate decarboxylase 2
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520 |a 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 
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650 7 |a Glutamate Decarboxylase  |2 NLM 
650 7 |a EC 4.1.1.15  |2 NLM 
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650 7 |a EC 4.1.1.15  |2 NLM 
700 1 |a Jiang, Xiaohua  |e verfasserin  |4 aut 
700 1 |a Zhao, Junpeng  |e verfasserin  |4 aut 
700 1 |a Duan, Deyi  |e verfasserin  |4 aut 
700 1 |a Zhao, Huanying  |e verfasserin  |4 aut 
700 1 |a Xu, Qunyuan  |e verfasserin  |4 aut 
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