Journal article
DNA plasmid that codes for human Bcl-2 gene preserves axotomized Clarke's nucleus neurons and reduces atrophy after spinal cord hemisection in adult rats
Journal of comparative neurology (1911), v 404(2)
08 Feb 1999
PMID: 9934991
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Spinal cord injury in adult mammals causes atrophy or death of some axotomized neurons. The product of the antiapoptotic gene Bcl-2 prevents neuron death in vivo. We delivered Bcl-2 by intraspinal injection of a DNA plasmid encoding this gene to determine if axotomized neurons destined to undergo retrograde death could be rescued. Axons of the right side Clarke's Nucleus (CN) were cut unilaterally in adult Sprague-Dawley rats by T8 hemisection, leaving the contralateral (left) CN as an intact control. Two months postoperatively, there was ∼35% loss of total CN neurons in the right L1 segment. Only 15% of large CN neurons (>400 μm2), whose axons project to the cerebellum, survived—indicating atrophy and/or death of 85% of these cells. We injected a DNA plasmid encoding the human Bcl-2 gene and the bacterial reporter gene LacZ, which was complexed with cationic lipids, into the right side of segment T8 of the normal spinal cord, or just caudal to the hemisection site. The reporter gene was expressed in the perikarya of right CN neurons at L1 for up to 7 days, but not 14 days. Two months following T8 hemisection and Bcl-2/LacZ DNA injection, there was no significant loss of CN neurons ipsilateral to the lesion. Surprisingly, 61% of large neurons survived, indicating partial protection from atrophy. In contrast, a DNA plasmid that codes for the LacZ reporter gene, but not Bcl-2, did not prevent CN neuron death or atrophy. Administration of the Bcl-2 gene in adult rats and its expression in these CNS neurons prevents retrograde cell death, and also minimizes atrophy. These results may serve as the basis for developing novel gene therapy strategies for patients with spinal cord injury.
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Details
- Title
- DNA plasmid that codes for human Bcl-2 gene preserves axotomized Clarke's nucleus neurons and reduces atrophy after spinal cord hemisection in adult rats
- Creators
- Kosei Takahashi - Drexel University, Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)Emily Schwarz - Drexel University, Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)Cecilia Ljubetic - Drexel University, Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)Marion Murray - Drexel University, Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)Alan Tessler - Drexel University, Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)Raul A. Saavedra - Drexel University, Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Publication Details
- Journal of comparative neurology (1911), v 404(2)
- Publisher
- John Wiley & Sons, Inc
- Number of pages
- 13
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000078137900002
- Scopus ID
- 2-s2.0-0033535123
- Other Identifier
- 991019168472804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences
- Zoology