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

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 und...

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Veröffentlicht in:	Gene therapy 2007-03, Vol.14 (5), p.441-450
Hauptverfasser:	Do Thi, N A, Saillour, P, Ferrero, L, Paunio, T, Mallet, J
Format:	Artikel
Sprache:	eng
Schlagworte:	Adenoviridae Adenoviridae - genetics Adenovirus Amphetamines Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Applied cell therapy and gene therapy Astrocytes Astrocytes - metabolism Biochemistry, Molecular Biology Biological and medical sciences Biomedical and Life Sciences Biomedicine Biotechnology Cell Biology Cells, Cultured Central nervous system Corpus Striatum Corpus Striatum - metabolism Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Dopamine Dopamine - metabolism Dopamine receptors Female Fundamental and applied biological sciences. Psychology Gene Expression Gene Therapy Genetic aspects Genetic Therapy - methods Genetic Vectors Genetic Vectors - administration & dosage Glial Cell Line-Derived Neurotrophic Factor Glial Cell Line-Derived Neurotrophic Factor - genetics Glial Cell Line-Derived Neurotrophic Factor - metabolism Glial cells Health aspects Health. Pharmaceutical industry Human Genetics Industrial applications and implications. Economical aspects Life Sciences Medical sciences Mesencephalon Mesencephalon - metabolism Methods Movement disorders Nanotechnology Neostriatum Neurodegenerative diseases Neurology Neuronal-glial interactions Neurons Neurons - metabolism original-article Parkinson Disease Parkinson Disease - metabolism Parkinson's disease Phosphopyruvate Hydratase Phosphopyruvate Hydratase - genetics Promoter Regions (Genetics) Promoter Regions, Genetic Rats Rats, Sprague-Dawley Rodents Rotational behavior Substantia Nigra Substantia Nigra - metabolism Transduction, Genetic Transduction, Genetic - methods Transfusions. Complications. Transfusion reactions. Cell and gene therapy Transgenes
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Zusammenfassung:	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.
ISSN:	0969-7128 1476-5462
DOI:	10.1038/sj.gt.3302844