{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/79316"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/79316","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Characterization of Metabolic Activity in Schwann Cells for Axon Survival During Wallerian Degeneration","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Wong, Keit Men; 0000-0002-5449-6318"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Beirowski, Bogdan","Neuroscience"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-04-04T17:49:00Z","date_published":"2019-04-04T17:49:00Z","updated_at":"2026-07-27T19:05:14Z","subjects":["neurosciences"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/79316","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Beirowski, Bogdan","Neuroscience"]},{"key":"dc:creator","label":"Author","values":["Wong, Keit Men; 0000-0002-5449-6318"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-04-04T17:49:00Z","2019","2019-01-10 22:59:53"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["neurosciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/79316"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","The degeneration of injured axons with concomitant alterations in their flanking glia (Schwann cells in the PNS and oligodendrocytes in the CNS) is a central hallmark of a wide range of neurodegenerative conditions. The cellular and molecular mechanisms of axonal degeneration and whether they are primarily regulated by cell autonomous or non-cell autonomous factors are poorly understood. Emerging evidence suggests that oligodendrocytes support axons dynamically through their glucose metabolism by differential release of small carbohydrates which are then taken up by axons to meet axonal bioenergetics needs. However, the existing evidence for such glial support mechanisms provided by SCs in the PNS is scarce to non-existent. How SCs may adjust their glucose mechanism to support distressed and injured axons is unknown. To shed light on this void, I used Wallerian degeneration (WD) as a straightforward experimental model system to study the injury and degeneration responses of axons and their SC glia. WD occurs after axons are separated from their parent neuronal cell bodies. Here I studied how SCs adapt their glucose metabolism to axonal injury and whether such adaptations support axon integrity in the context of WD.In this dissertation, I present data for the first time demonstrating that the presence of SCs delays axonal degeneration during WD. Such SCs undergo striking metabolic reprogramming during WD with dramatic increases of GLUT1-mediated glucose uptake and elevated expression and activity of glycolytic regulatory enzymes. Reducing the enhanced glycolytic response in SCs by genetic manipulations markedly accelerates the degeneration of injured axons. Intriguingly, I found that the glycolytic conversion in SCs is controlled by the metabolic signaling hub mammalian target of rapamycin complex 1 (mTORC1) and its downstream glycolytic regulator Hif1α. Strikingly, boosting mTORC1 activity in SCs delays axonal loss while suppression of the mTORC1-dependent metabolic rewiring in SCs leads to faster axonal disintegration during WD. Thus, I demonstrate evidence for a non-cell autonomous mechanism of axonal support function through enhanced glycolytic reprogramming in SCs. Such injury-activated SCs may transfer pyruvate/lactate through monocarboxylate transporters into the axonal compartment, and this function may be essential to stabilize distressed axons in various degeneration circumstances. These and other questions are currently investigated in my host laboratory. Together, this study highlights the intriguing links between central metabolic signaling pathways in Schwann cell glia and compartmentalized neurodegeneration. The findings improve our understanding of non-cell-autonomous mechanisms of axon degeneration, and have the potential to lead to novel treatment strategies for neurodegenerative conditions with prominent axonal degeneration components."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Characterization of Metabolic Activity in Schwann Cells for Axon Survival During Wallerian Degeneration"]}]}],"canonical_facts":{"dc:contributor":["Beirowski, Bogdan","Neuroscience"],"dc:creator":["Wong, Keit Men; 0000-0002-5449-6318"],"dc:date":["2019-04-04T17:49:00Z","2019","2019-01-10 22:59:53"],"dc:description":["Ph.D.","The degeneration of injured axons with concomitant alterations in their flanking glia (Schwann cells in the PNS and oligodendrocytes in the CNS) is a central hallmark of a wide range of neurodegenerative conditions. The cellular and molecular mechanisms of axonal degeneration and whether they are primarily regulated by cell autonomous or non-cell autonomous factors are poorly understood. Emerging evidence suggests that oligodendrocytes support axons dynamically through their glucose metabolism by differential release of small carbohydrates which are then taken up by axons to meet axonal bioenergetics needs. However, the existing evidence for such glial support mechanisms provided by SCs in the PNS is scarce to non-existent. How SCs may adjust their glucose mechanism to support distressed and injured axons is unknown. To shed light on this void, I used Wallerian degeneration (WD) as a straightforward experimental model system to study the injury and degeneration responses of axons and their SC glia. WD occurs after axons are separated from their parent neuronal cell bodies. Here I studied how SCs adapt their glucose metabolism to axonal injury and whether such adaptations support axon integrity in the context of WD.In this dissertation, I present data for the first time demonstrating that the presence of SCs delays axonal degeneration during WD. Such SCs undergo striking metabolic reprogramming during WD with dramatic increases of GLUT1-mediated glucose uptake and elevated expression and activity of glycolytic regulatory enzymes. Reducing the enhanced glycolytic response in SCs by genetic manipulations markedly accelerates the degeneration of injured axons. Intriguingly, I found that the glycolytic conversion in SCs is controlled by the metabolic signaling hub mammalian target of rapamycin complex 1 (mTORC1) and its downstream glycolytic regulator Hif1α. Strikingly, boosting mTORC1 activity in SCs delays axonal loss while suppression of the mTORC1-dependent metabolic rewiring in SCs leads to faster axonal disintegration during WD. Thus, I demonstrate evidence for a non-cell autonomous mechanism of axonal support function through enhanced glycolytic reprogramming in SCs. Such injury-activated SCs may transfer pyruvate/lactate through monocarboxylate transporters into the axonal compartment, and this function may be essential to stabilize distressed axons in various degeneration circumstances. These and other questions are currently investigated in my host laboratory. Together, this study highlights the intriguing links between central metabolic signaling pathways in Schwann cell glia and compartmentalized neurodegeneration. The findings improve our understanding of non-cell-autonomous mechanisms of axon degeneration, and have the potential to lead to novel treatment strategies for neurodegenerative conditions with prominent axonal degeneration components."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/79316"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["neurosciences"],"dc:title":["Characterization of Metabolic Activity in Schwann Cells for Axon Survival During Wallerian Degeneration"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:14Z"}