Subthalamic hGAD65 gene therapy and striatum TH gene transfer in a Parkinson's disease rat model.
Neural Plast
; 2013: 263287, 2013.
Article
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| MEDLINE
| ID: mdl-23738148
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson Secundaria
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Tirosina 3-Monooxigenasa
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Terapia Genética
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Técnicas de Transferencia de Gen
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Cuerpo Estriado
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Núcleo Subtalámico
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Glutamato Descarboxilasa
Límite:
Animals
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Humans
Idioma:
En
Revista:
Neural Plast
Asunto de la revista:
NEUROLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
China