DOI: 10.1073/pnas.96.7.4078. Herpes simplex virus vector-mediated expression of Bcl-2 prevents 6-hydroxydopamine-induced degeneration of neurons in the substantia nigra <i>in vivo</i>

Herpes simplex virus vector-mediated expression of Bcl-2 prevents 6-hydroxydopamine-induced degeneration of neurons in the substantia nigra in vivo

10.1073/pnas.96.7.4078

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

6-Hydroxydopamine (6-OHDA) is widely used to selectively lesion dopaminergic neurons of the substantia nigra (SN) in the creation of animal models of Parkinson’s disease. In vitro , the death of PC-12 cells caused by exposure to 6-OHDA occurs with characteristics consistent with an apoptotic mechanism of cell death. To test the hypothesis that apoptotic pathways are involved in the death of dopaminergic neurons of the SN caused by 6-OHDA, we created a replication-defective genomic herpes simplex virus-based vector containing the coding sequence for the antiapoptotic peptide Bcl-2 under the transcriptional control of the simian cytomegalovirus immediate early promoter. Transfection of primary cortical neurons in culture with the Bcl-2-producing vector protected those cells from naturally occurring cell death over 3 weeks. Injection of the Bcl-2-expressing vector into SN of rats 1 week before injection of 6-OHDA into the ipsilateral striatum increased the survival of neurons in the SN, detected either by retrograde labeling of those cells with fluorogold or by tyrosine hydroxylase immunocytochemistry, by 50%. These results, demonstrating that death of nigral neurons induced by 6-OHDA lesioning may be blocked by the expression of Bcl-2, are consistent with the notion that cell death in this model system is at least in part apoptotic in nature and suggest that a Bcl-2-expressing vector may have therapeutic potential in the treatment of Parkinson’s disease.

Bibliography

Yamada, M., Oligino, T., Mata, M., Goss, J. R., Glorioso, J. C., & Fink, D. J. (1999). Herpes simplex virus vector-mediated expression of Bcl-2 prevents 6-hydroxydopamine-induced degeneration of neurons in the substantia nigra in vivo. Proceedings of the National Academy of Sciences, 96(7), 4078â4083.

Authors 6

Masanobu Yamada (first)
Thomas Oligino (additional)
Marina Mata (additional)
James R. Goss (additional)
Joseph C. Glorioso (additional)
David J. Fink (additional)

References 43 Referenced 93

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Dates

Type	When
Created	23 years ago (July 26, 2002, 10:42 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 5:45 p.m.)
Indexed	1 year ago (Aug. 7, 2024, 1:51 p.m.)
Issued	26 years, 4 months ago (March 30, 1999)
Published	26 years, 4 months ago (March 30, 1999)
Published Online	26 years, 4 months ago (March 30, 1999)
Published Print	26 years, 4 months ago (March 30, 1999)

Funders 0

None

BibTeX

@article{Yamada_1999, title={Herpes simplex virus vector-mediated expression of Bcl-2 prevents 6-hydroxydopamine-induced degeneration of neurons in the substantia nigra in vivo}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.7.4078}, DOI={10.1073/pnas.96.7.4078}, number={7}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Yamada, Masanobu and Oligino, Thomas and Mata, Marina and Goss, James R. and Glorioso, Joseph C. and Fink, David J.}, year={1999}, month=mar, pages={4078–4083} }

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