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Molecular and cellular events associated with damage to rat retinal ganglion cells: Effects of brain-derived neurotrophic factor on fast axonal transport and neuronal apoptosis

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Date Issued:
1998
Summary:
The survival of rat retinal ganglion cells (RGCs) after axotomy has been shown to be enhanced by Brain Derived Neurotrophic Factor (BDNF). It was, therefore, of interest to determine whether previously observed changes in the differential regulation of fast axonally transported proteins (FTPs) occur in rat RGCs during the early response to axotomy or whether such changes are obviated by the action of BDNF at the cell body level. It was of further interest to determine whether these regeneration-associated changes are sustained during the period of BDNF-enhanced cell survival. It was found that, within 2 days of injury and BDNF injection, rat RGCs initiate a growth-like cellular response that includes the differential synthesis and transport of the same profile of FTPs found to be induced in axotomized animals following injection of a saline control solution. Thus, supplementation of rat RGCs with BDNF does not obviate the changes required to reinstate active cellular regrowth. It is, therefore, unlikely that the loss of a trophic factor, such as BDNF, is the signal for axotomy-induced changes. Although a single injection of BDNF at the time of injury prolongs cell survival to at least 5 days, it is not sufficient to sustain the elevation in FTPs. This result indicates that the regulatory mechanisms that promote cell growth are distinct and separate from those that promote cell survival. This study extended beyond the above findings to affirm that apoptosis of axotomized rat RGCs is mediated by the activation of the cysteine protease, caspase-3. Such activation was demonstrated within 12 hours of axotomy and appeared to become increasingly prevalent in a central to peripheral gradient, as might be anticipated by the loss of glial derived neurotrophic support. Such activation was completely prevented by intraocular injection of BDNF, indicating that BDNF acts upstream of caspase-3 to prevent the proteolytic cascade that leads to apoptosis.
Title: Molecular and cellular events associated with damage to rat retinal ganglion cells: Effects of brain-derived neurotrophic factor on fast axonal transport and neuronal apoptosis.
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Name(s): Wodarczyk, Linda
Florida Atlantic University, Degree Grantor
Charles E. Schmidt College of Science
Center for Complex Systems and Brain Sciences
Type of Resource: text
Genre: Electronic Thesis Or Dissertation
Issuance: monographic
Date Issued: 1998
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: application/pdf
Extent: 285 p.
Language(s): English
Summary: The survival of rat retinal ganglion cells (RGCs) after axotomy has been shown to be enhanced by Brain Derived Neurotrophic Factor (BDNF). It was, therefore, of interest to determine whether previously observed changes in the differential regulation of fast axonally transported proteins (FTPs) occur in rat RGCs during the early response to axotomy or whether such changes are obviated by the action of BDNF at the cell body level. It was of further interest to determine whether these regeneration-associated changes are sustained during the period of BDNF-enhanced cell survival. It was found that, within 2 days of injury and BDNF injection, rat RGCs initiate a growth-like cellular response that includes the differential synthesis and transport of the same profile of FTPs found to be induced in axotomized animals following injection of a saline control solution. Thus, supplementation of rat RGCs with BDNF does not obviate the changes required to reinstate active cellular regrowth. It is, therefore, unlikely that the loss of a trophic factor, such as BDNF, is the signal for axotomy-induced changes. Although a single injection of BDNF at the time of injury prolongs cell survival to at least 5 days, it is not sufficient to sustain the elevation in FTPs. This result indicates that the regulatory mechanisms that promote cell growth are distinct and separate from those that promote cell survival. This study extended beyond the above findings to affirm that apoptosis of axotomized rat RGCs is mediated by the activation of the cysteine protease, caspase-3. Such activation was demonstrated within 12 hours of axotomy and appeared to become increasingly prevalent in a central to peripheral gradient, as might be anticipated by the loss of glial derived neurotrophic support. Such activation was completely prevented by intraocular injection of BDNF, indicating that BDNF acts upstream of caspase-3 to prevent the proteolytic cascade that leads to apoptosis.
Identifier: 9780599117174 (isbn), 12586 (digitool), FADT12586 (IID), fau:9472 (fedora)
Collection: FAU Electronic Theses and Dissertations Collection
Note(s): Adviser: Gary W. Perry.
Thesis (Ph.D.)--Florida Atlantic University, 1998.
Subject(s): Biology, Neuroscience
Biology, Cell
Persistent Link to This Record: http://purl.flvc.org/fcla/dt/12586
Use and Reproduction: Copyright © is held by the author, with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.
Use and Reproduction: http://rightsstatements.org/vocab/InC/1.0/
Host Institution: FAU
Is Part of Series: Florida Atlantic University Digital Library Collections.