Theaimof the present study is to detect a combination method to utilize gene therapy for the treatment of Parkinson�s disease (PD).\r\nHere, a PD rat model is used for the in vivo gene therapy of a recombinant adeno-associated virus (AAV2) containing a human\r\nglutamic acid decarboxylase 65 (rAAV2-hGAD65) gene delivered to the subthalamic nucleus (STN). This is combined with the ex\r\nvivo gene delivery of tyrosine hydroxylase (TH) by fibroblasts injected into the striatum. After the treatment, the rotation behavior\r\nwas improved with the greatest efficacy in the combination group. The results of immunohistochemistry showed that hGAD65\r\ngene delivery by AAV2 successfully led to phenotypic changes of neurons in STN. And the levels of glutamic acid and GABA in\r\nthe internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr) were obviously lower than the control\r\ngroups. However, hGAD65 gene transfer did not effectively protect surviving dopaminergic neurons in the SNc and VTA. This\r\nstudy suggests that subthalamic hGAD65 gene therapy and combined with TH gene therapy can alleviate symptoms of the PD\r\nmodel rats, independent of the protection the DA neurons from death.
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