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Delivery of GDNF by an E1,E3/E4 deleted adenoviral vector and driven by a GFAP promoter prevents dopaminergic neuron degeneration in a rat model of Parkinson's disease.
Gene Ther. 2004 May; 11(9):746-56.GT

Abstract

A new adenoviral vector (Ad-GFAP-GDNF) (Ad=adenovirus, GFAP=glial fibrillary acidic protein, GDNF=glial cell line-derived neurotrophic factor) was constructed in which (i) the E1,E3/E4 regions of Ad5 were deleted and (ii) the GDNF transgene is driven by the GFAP promoter. We verified, in vitro, that the recombinant GDNF was expressed in primary cultures of astrocytes. In vivo, the Ad-GFAP-GDNF was injected into the striatum of rats 1 week before provoking striatal 6-OHDA lesion. After 1 month, the striatal GDNF levels were 37 pg/microg total protein. This quantity was at least 120-fold higher than in nontransduced striatum or after injection of the empty adenoviral vector. At 3 months after viral injection, GDNF expression decreased, whereas the viral DNA remained unchanged. Furthermore, around 70% of the dopaminergic (DA) neurons were protected from degeneration up to 3 months as compared to about 45% in the control groups. In addition, the amphetamine-induced rotational behavior was decreased. The results obtained in this study on DA neuron protection and rotational behavior are similar to those previously reported using vectors with viral promoters. In addition to these results, we established that a high level of GDNF was present in the striatum and that the period of GDNF expression was prolonged after injection of our adenoviral vector.

Authors+Show Affiliations

Laboratoire de Genetique Moleculaire de la Neurotransmission et des Processus Neurodegeneratifs, CNRS, Bat. CERVI, Hopital Pitie-Salpetriere, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14724667

Citation

Do Thi, N A., et al. "Delivery of GDNF By an E1,E3/E4 Deleted Adenoviral Vector and Driven By a GFAP Promoter Prevents Dopaminergic Neuron Degeneration in a Rat Model of Parkinson's Disease." Gene Therapy, vol. 11, no. 9, 2004, pp. 746-56.
Do Thi NA, Saillour P, Ferrero L, et al. Delivery of GDNF by an E1,E3/E4 deleted adenoviral vector and driven by a GFAP promoter prevents dopaminergic neuron degeneration in a rat model of Parkinson's disease. Gene Ther. 2004;11(9):746-56.
Do Thi, N. A., Saillour, P., Ferrero, L., Dedieu, J. F., Mallet, J., & Paunio, T. (2004). Delivery of GDNF by an E1,E3/E4 deleted adenoviral vector and driven by a GFAP promoter prevents dopaminergic neuron degeneration in a rat model of Parkinson's disease. Gene Therapy, 11(9), 746-56.
Do Thi NA, et al. Delivery of GDNF By an E1,E3/E4 Deleted Adenoviral Vector and Driven By a GFAP Promoter Prevents Dopaminergic Neuron Degeneration in a Rat Model of Parkinson's Disease. Gene Ther. 2004;11(9):746-56. PubMed PMID: 14724667.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Delivery of GDNF by an E1,E3/E4 deleted adenoviral vector and driven by a GFAP promoter prevents dopaminergic neuron degeneration in a rat model of Parkinson's disease. AU - Do Thi,N A, AU - Saillour,P, AU - Ferrero,L, AU - Dedieu,J F, AU - Mallet,J, AU - Paunio,T, PY - 2004/1/16/pubmed PY - 2004/6/29/medline PY - 2004/1/16/entrez SP - 746 EP - 56 JF - Gene therapy JO - Gene Ther VL - 11 IS - 9 N2 - A new adenoviral vector (Ad-GFAP-GDNF) (Ad=adenovirus, GFAP=glial fibrillary acidic protein, GDNF=glial cell line-derived neurotrophic factor) was constructed in which (i) the E1,E3/E4 regions of Ad5 were deleted and (ii) the GDNF transgene is driven by the GFAP promoter. We verified, in vitro, that the recombinant GDNF was expressed in primary cultures of astrocytes. In vivo, the Ad-GFAP-GDNF was injected into the striatum of rats 1 week before provoking striatal 6-OHDA lesion. After 1 month, the striatal GDNF levels were 37 pg/microg total protein. This quantity was at least 120-fold higher than in nontransduced striatum or after injection of the empty adenoviral vector. At 3 months after viral injection, GDNF expression decreased, whereas the viral DNA remained unchanged. Furthermore, around 70% of the dopaminergic (DA) neurons were protected from degeneration up to 3 months as compared to about 45% in the control groups. In addition, the amphetamine-induced rotational behavior was decreased. The results obtained in this study on DA neuron protection and rotational behavior are similar to those previously reported using vectors with viral promoters. In addition to these results, we established that a high level of GDNF was present in the striatum and that the period of GDNF expression was prolonged after injection of our adenoviral vector. SN - 0969-7128 UR - https://www.unboundmedicine.com/medline/citation/14724667/Delivery_of_GDNF_by_an_E1E3/E4_deleted_adenoviral_vector_and_driven_by_a_GFAP_promoter_prevents_dopaminergic_neuron_degeneration_in_a_rat_model_of_Parkinson's_disease_ L2 - https://doi.org/10.1038/sj.gt.3302222 DB - PRIME DP - Unbound Medicine ER -