| Inhibition of caspase-3-mediated apoptosis improves spinal cord repair in a regeneration-competent vertebrate system. | |
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MedLine Citation:
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PMID: 20837106 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Teleost fish exhibit an excellent potential for structural and functional recovery after CNS lesions. The function of apoptosis in the process of regeneration remains controversial. While some studies have identified this type of cell death as essential for successful regeneration, other investigations have suggested some degree of functional improvement after inhibition of apoptosis. In the present study, we examined whether inhibition of apoptosis immediately after injury can improve spinal cord regeneration. As a model system, we used Apteronotus leptorhynchus, a regeneration-competent weakly electric fish. To inhibit apoptosis, we employed 2,2'-methylenebis (1,3-cyclohexanedione) (M50054), a compound that prevents caspase-3 activation. Administration of this apoptosis inhibitor led to a significant reduction in the numbers of apoptotic cells at 24 h, 5 days, and 30 days after the lesion. Using triple immunolabeling, we identified a significant reduction in the level of apoptosis at 5 and 30 days after the lesion among the following cellular categories: cells generated shortly after the lesion, existing neurons, and newly differentiated neurons. This reduced rate of apoptosis led to an increase in the relative number of differentiating and surviving neurons at both 5 and 30 days post-injury, compared to the control groups. Functional regeneration, as indicated by the recovery rate of the amplitude of the electric organ discharge (EOD), was significantly improved within the first 20 days after the lesion in the fish treated with M50054. Our data provide the first evidence that modulation of caspase-3 activation can significantly improve neuroregeneration and functional recovery in a regeneration-competent organism. |
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Authors:
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R F Sîrbulescu; G K H Zupanc |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-16 |
Journal Detail:
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Title: Neuroscience Volume: 171 ISSN: 1873-7544 ISO Abbreviation: Neuroscience Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-08 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7605074 Medline TA: Neuroscience Country: United States |
Other Details:
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Languages: eng Pagination: 599-612 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved. |
Affiliation:
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School of Engineering and Science, Jacobs University Bremen, P.O. BOX 750 561, 28725 Bremen, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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