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Bcl-2 and GDNF delivered by HSV-mediated gene transfer act additively to protect dopaminergic neurons from 6-OHDA-induced degeneration.
Exp Neurol. 2001 Jun; 169(2):231-8.EN

Abstract

Previous studies have demonstrated that either the neurotrophin glial-derived neurotrophic factor (GDNF) or the antiapoptotic peptide Bcl-2 delivered into striatum by a viral vector protects dopaminergic neurons of the substantia nigra in vivo from degeneration induced by the administration of the neurotoxin 6-hydroxydopamine (6-OHDA). In this study we used recombinant, replication-incompetent, genomic herpes simplex virus-based vectors to deliver the genes coding for Bcl-2 and GDNF into rat substantia nigra (SN) 1 week prior to 6-OHDA injection into the striatum. Vector-mediated expression of either Bcl-2 or GDNF alone each resulted in a doubling in cell survival as measured by retrograde labeling with fluorogold (FG) and a 50% increase in tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the lesioned SN compared to the unlesioned side. Gene transfer of Bcl-2 and GDNF were equivalent in this effect. Coadministration of the Bcl-2-expressing vector with the GDNF-expressing vector improved the survival of lesioned SN neurons as measured by FG labeling by 33% and by the expression of TH-IR by 15%. These results suggest that the two factors delivered together act in an additive fashion to improve DA cell survival in the face of 6-OHDA toxicity.

Authors+Show Affiliations

Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11358438

Citation

Natsume, A, et al. "Bcl-2 and GDNF Delivered By HSV-mediated Gene Transfer Act Additively to Protect Dopaminergic Neurons From 6-OHDA-induced Degeneration." Experimental Neurology, vol. 169, no. 2, 2001, pp. 231-8.
Natsume A, Mata M, Goss J, et al. Bcl-2 and GDNF delivered by HSV-mediated gene transfer act additively to protect dopaminergic neurons from 6-OHDA-induced degeneration. Exp Neurol. 2001;169(2):231-8.
Natsume, A., Mata, M., Goss, J., Huang, S., Wolfe, D., Oligino, T., Glorioso, J., & Fink, D. J. (2001). Bcl-2 and GDNF delivered by HSV-mediated gene transfer act additively to protect dopaminergic neurons from 6-OHDA-induced degeneration. Experimental Neurology, 169(2), 231-8.
Natsume A, et al. Bcl-2 and GDNF Delivered By HSV-mediated Gene Transfer Act Additively to Protect Dopaminergic Neurons From 6-OHDA-induced Degeneration. Exp Neurol. 2001;169(2):231-8. PubMed PMID: 11358438.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bcl-2 and GDNF delivered by HSV-mediated gene transfer act additively to protect dopaminergic neurons from 6-OHDA-induced degeneration. AU - Natsume,A, AU - Mata,M, AU - Goss,J, AU - Huang,S, AU - Wolfe,D, AU - Oligino,T, AU - Glorioso,J, AU - Fink,D J, PY - 2001/5/19/pubmed PY - 2001/7/6/medline PY - 2001/5/19/entrez SP - 231 EP - 8 JF - Experimental neurology JO - Exp Neurol VL - 169 IS - 2 N2 - Previous studies have demonstrated that either the neurotrophin glial-derived neurotrophic factor (GDNF) or the antiapoptotic peptide Bcl-2 delivered into striatum by a viral vector protects dopaminergic neurons of the substantia nigra in vivo from degeneration induced by the administration of the neurotoxin 6-hydroxydopamine (6-OHDA). In this study we used recombinant, replication-incompetent, genomic herpes simplex virus-based vectors to deliver the genes coding for Bcl-2 and GDNF into rat substantia nigra (SN) 1 week prior to 6-OHDA injection into the striatum. Vector-mediated expression of either Bcl-2 or GDNF alone each resulted in a doubling in cell survival as measured by retrograde labeling with fluorogold (FG) and a 50% increase in tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the lesioned SN compared to the unlesioned side. Gene transfer of Bcl-2 and GDNF were equivalent in this effect. Coadministration of the Bcl-2-expressing vector with the GDNF-expressing vector improved the survival of lesioned SN neurons as measured by FG labeling by 33% and by the expression of TH-IR by 15%. These results suggest that the two factors delivered together act in an additive fashion to improve DA cell survival in the face of 6-OHDA toxicity. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/11358438/Bcl_2_and_GDNF_delivered_by_HSV_mediated_gene_transfer_act_additively_to_protect_dopaminergic_neurons_from_6_OHDA_induced_degeneration_ DB - PRIME DP - Unbound Medicine ER -