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NON-APOPTOTIC INVOLVEMENT OF CASPASES IN ASTROGLIOSIS
by
Radha V. Aras
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(NEUROSCIENCE)
December 2006
Copyright 2006 Radha V. Aras
Object Description
| Title | Non-apoptotic involvement of caspases in astrogliosis |
| Author | Aras, Radha V. |
| Author email | radha.aras@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Thesis |
| Degree program | Neuroscience |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2006-01-03 |
| Date submitted | 2006 |
| Restricted until | Unrestricted |
| Date published | 2006-10-12 |
| Advisor (committee chair) | Pike, Christian J. |
| Advisor (committee member) |
Finch, Caleb Ko, Chieng-Ping Baudry, Michel Tower, John |
| Abstract | Astrogliosis is a characteristic response of astrocytes to almost all forms of brain injury. Despite being studied extensively, the molecular basis of astrogliosis remains largely unknown. This dissertation investigates caspases as potential signaling molecules involved in mediating astrocyte reactivity. Chapter 2 documents data from two different experimental models of astrogliosis supporting the hypothesis of a non-apoptotic involvement of caspases in astrogliosis. Our results show astrocytes made reactive by treatment with dibutryl cAMP and Aß[superscript 25-35], demonstrate an increase in total caspase activity with a corresponding increase in the expression of active pro-apoptotic caspase-3 in the absence of cell death. In addition, caspase inhibition by zVAD, a broadspectrum caspase inhibitor resulted in a partial attenuation of the increased expressions of two known markers of reactivity, glutamine synthetase and fibroblast growth factor-2, thus suggesting a non-apoptotic role for caspases in mediating astrogliosis. We further extended the study to an ex-vivo model of astrogliosis, comprising of adult hippocampal astrocyte cultures generated from kainate-lesioned rats. Astrocytes from the kainate-lesioned animals exhibited reactive features in culture, and a non-apoptotic caspase activation similar to that observed in the in vitro model. Further, a preliminary analysis of the caspase family using specific inhibitors suggests caspase-11 and 3 might contribute to the caspase function in astrogliosis. Reactive astrocytes are known to upregulate expression of several different proteins with important functional consequences on the injured brain. Chapter 3 investigates two major outcomes: neurite outgrowth and neuronal survival following injury and how caspase activation in reactive astrocytes might influence them. Our findings suggest inhibition of neurite growth on reactive astrocytes might be partly caspase-dependent. |
| Keyword | reactive astrocytes; zVAD; caspase; neurite growth; kainate; Aß |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m93 |
| Rights | Aras, Radha V. |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Aras-20061012 |
| Archival file | uscthesesreloadpub_Volume26/etd-Aras-20061012.pdf |
Description
| Title | Page 1 |
| Full text | NON-APOPTOTIC INVOLVEMENT OF CASPASES IN ASTROGLIOSIS by Radha V. Aras A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) December 2006 Copyright 2006 Radha V. Aras |
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