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Does neuronal expression of GDNF effectively protect dopaminergic neurons in a rat model of Parkinson's disease?

Abstract

The transfer of the Glial cell line-derived neurotrophic factor (GDNF) gene to the central nervous system by a recombinant adenoviral vector (Ad) was studied. We constructed the adenovirus vector Ad-NSE-GDNF from which the E1, E3/E4 regions of Ad5 have been deleted and in which the GDNF gene was under the control of a neuron-specific enolase (NSE) promoter. The vector was injected into the striatum of a rat model of Parkinson's disease. We found that (i) the NSE promoter can restrict transgene expression in neurons; (ii) Ad-NSE-GDNF significantly protected dopaminergic (DA) neurons in the substantia nigra (SN) but did not reverse the impairments of amphetamine-induced rotational behavior in lesioned rats.

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Acknowledgements

We thank Professor H Koenig for helpful discussions, and J Formentin for animal care. We thank the Vector Core of the University Hospital of Nantes supported by the Association Française Contre les Myopathies (AFM) for providing the AAV vectors. This work was supported by Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie, Paris 6 and Institut pour la Recherche sur la Moelle Epiniere et l’Encephale (IRME), France.

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Do Thi, N., Saillour, P., Ferrero, L. et al. Does neuronal expression of GDNF effectively protect dopaminergic neurons in a rat model of Parkinson's disease?. Gene Ther 14, 441–450 (2007). https://doi.org/10.1038/sj.gt.3302844

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