{"id":{"repo_id":"rochester","oai_identifier":"oai:urresearch.rochester.edu:394"},"canonical_url":"https://search.dev.ndltd.org/etd/rochester/oai:urresearch.rochester.edu:394","repository":{"repo_id":"rochester","name":"Rochester University","base_url":"http://urresearch.rochester.edu/oai2.action"},"display":{"title":"Strategies for Neuroprotection Using Passive (Neurotrophin-Deprivation) and Active (Virotoxin Exposure) Models of Neuronal Cell Death","abstract":"Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Microbiology and Immunology, 2004.","abstract_html":"Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Microbiology and Immunology, 2004.","abstract_has_math":false,"creators":["Ramirez, Servio","Dewhurst, Stephen"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2004,"date_issued":"Mon, 2 Aug 2004 18:31:18","date_published":"Mon, 2 Aug 2004 18:31:18","updated_at":"2026-07-27T20:46:02Z","subjects":["Neurotrophin","NeuroAIDS"],"languages":["eng"],"rights":["This item is protected by copyright, with all rights reserved."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1802/541","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Ramirez, Servio","Dewhurst, Stephen"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["Mon, 2 Aug 2004 18:31:18","Month: 8 Day: 2 Year: 2004","Thu, 4 Dec 2025 16:13:24"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Neurotrophin","NeuroAIDS"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["This item is protected by copyright, with all rights reserved."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/1802/541"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Microbiology and Immunology, 2004.","The overall goal of this thesis was to examine the following hypothesis: that important molecular regulators of neural fate are shared between divergent experimental/cellular paradigms, and that the identification of such pathways might lead to new therapeutic insights for neurologic diseases, including neuroAIDS. In order to approach this hypothesis, I utilized two well-characterized, but highly divergent in vitro model systems: (i) toxin-induced apoptosis in CNS-derived neurons (as represented by exposure of cerebellar granule neurons [CGN] to HIV-1 Tat) and (ii) neurotrophin withdrawal-induced cell death in sympathetic neurons. Our laboratory had previously shown that the transcription factor NFκB was a survival factor for sympathetic neurons, and that continuous neurotrophin exposure was necessary to maintain high levels of NFκB activity in these cells. I therefore hypothesized that neurotrophin-mediated NFκB activation might also enhance the survival of Tat-exposed CGNs. Results presented in this thesis show that several different neurotrophins were indeed able to inhibit Tat-mediated neurotoxicity in CGN cells, via the activation of NFκB. Follow-up experiments revealed that NFκB’s protective effects were mediated in part via the activation of downstream target genes such as BCL-2, and in part by NFκB’s ability to successfully compete away key transcriptional coactivators (CBP/p300) from pro-apoptotic transcription factors such as Jun. In the final portion of this thesis, I returned to the NGF-deprivation paradigm in order to determine whether a small molecule with known neuroprotective activity in CNS-derived neurons (adenosine) might also enhance the survival of NGF-deprived sympathetic neurons. Experimental analysis revealed that adenosine did indeed enhance the survival of NGF-deprived sympathetic neurons, and that this effect could be reproduced by use of an A2A adenosine receptor subtype-specific agonist (CGS21680); the ERK1/2 (MAPK) pathway was also implicated as an important contributor to this survival-promoting effect. Overall, this thesis reveals important common pathways and regulators of neuronal cell fate; it is hoped that future work will successfully target these survival pathways in order to improve the outcomes of a range of neurologic diseases (including neuroAIDS)."]},{"key":"dc:title","label":"Title","values":["Strategies for Neuroprotection Using Passive (Neurotrophin-Deprivation) and Active (Virotoxin Exposure) Models of Neuronal Cell Death"]}]}],"canonical_facts":{"dc:creator":["Ramirez, Servio","Dewhurst, Stephen"],"dc:date":["Mon, 2 Aug 2004 18:31:18","Month: 8 Day: 2 Year: 2004","Thu, 4 Dec 2025 16:13:24"],"dc:description":["Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Microbiology and Immunology, 2004.","The overall goal of this thesis was to examine the following hypothesis: that important molecular regulators of neural fate are shared between divergent experimental/cellular paradigms, and that the identification of such pathways might lead to new therapeutic insights for neurologic diseases, including neuroAIDS. In order to approach this hypothesis, I utilized two well-characterized, but highly divergent in vitro model systems: (i) toxin-induced apoptosis in CNS-derived neurons (as represented by exposure of cerebellar granule neurons [CGN] to HIV-1 Tat) and (ii) neurotrophin withdrawal-induced cell death in sympathetic neurons. Our laboratory had previously shown that the transcription factor NFκB was a survival factor for sympathetic neurons, and that continuous neurotrophin exposure was necessary to maintain high levels of NFκB activity in these cells. I therefore hypothesized that neurotrophin-mediated NFκB activation might also enhance the survival of Tat-exposed CGNs. Results presented in this thesis show that several different neurotrophins were indeed able to inhibit Tat-mediated neurotoxicity in CGN cells, via the activation of NFκB. Follow-up experiments revealed that NFκB’s protective effects were mediated in part via the activation of downstream target genes such as BCL-2, and in part by NFκB’s ability to successfully compete away key transcriptional coactivators (CBP/p300) from pro-apoptotic transcription factors such as Jun. In the final portion of this thesis, I returned to the NGF-deprivation paradigm in order to determine whether a small molecule with known neuroprotective activity in CNS-derived neurons (adenosine) might also enhance the survival of NGF-deprived sympathetic neurons. Experimental analysis revealed that adenosine did indeed enhance the survival of NGF-deprived sympathetic neurons, and that this effect could be reproduced by use of an A2A adenosine receptor subtype-specific agonist (CGS21680); the ERK1/2 (MAPK) pathway was also implicated as an important contributor to this survival-promoting effect. Overall, this thesis reveals important common pathways and regulators of neuronal cell fate; it is hoped that future work will successfully target these survival pathways in order to improve the outcomes of a range of neurologic diseases (including neuroAIDS)."],"dc:identifier":["http://hdl.handle.net/1802/541"],"dc:language":["eng"],"dc:rights":["This item is protected by copyright, with all rights reserved."],"dc:subject":["Neurotrophin","NeuroAIDS"],"dc:title":["Strategies for Neuroprotection Using Passive (Neurotrophin-Deprivation) and Active (Virotoxin Exposure) Models of Neuronal Cell Death"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T20:46:02Z"}