{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/80609"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/80609","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"The Role of Ferritin and Transferrin Receptor in Oligodendrocyte Maturation and Myelination","abstract":"M.S.","abstract_html":"M.S.","abstract_has_math":false,"creators":["Wan, Rensheng"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Paez, Pablo","Pharmacology and Toxicology"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-10-28T19:53:09Z","date_published":"2019-10-28T19:53:09Z","updated_at":"2026-07-27T19:05:23Z","subjects":["pharmacology"],"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/10477/80609","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Paez, Pablo","Pharmacology and Toxicology"]},{"key":"dc:creator","label":"Author","values":["Wan, Rensheng"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-10-28T19:53:09Z","2019","2019-05-29 11:20:05"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["pharmacology"]}]},{"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/10477/80609"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["M.S.","There is a critical relationship between oligodendrocyte (OL) development, myelin production and iron. Iron deficiency leads to hypomyelination both in humans and animal models, and the neurological sequelae of hypomyelination are significant. Therefore, understanding the molecular mechanisms of iron uptake and storage in OLs is necessary for planning effective strategies for iron supplementation. Ferritin is an intracellular protein that stores iron and releases it in a controlled fashion. Even though ferritin is highly express by oligodendrocyte progenitor cells (OPCs), nothing is known about the role of ferritin on OPC maturation and myelination. To determine whether ferritin is required for OPC maturation, we used the Cre-lox system to knock-out ferritin expression in vitro as well as in vivo. Blocking ferritin production reduce OPC iron uptake and significantly delay OPC development in primary cultures. In vivo, a significant hypomyelination was found in conditional knock-out mice in which ferritin was postnatally deleted in Sox10 positive OPCs. The brain of ferritin knock-out animals presented an important decrease in the expression levels of myelin proteins and a substantial reduction in the percentage of myelinated axons. This reduced postnatal myelination was accompanied by a significant decrease in the number of myelinating OLs and with a reduction in proliferating OPCs. These results indicate that ferritin is important for an appropriate OPC maturation and suggest that this iron storage protein is essential for the normal myelination of the mouse brain. We have also performed similar experiments in a conditional knock-out mouse in which the transferrin receptor 1 was deleted in OPCs. In this animals, the ablation of the transferrin receptor 1 in Sox10 positive OPCs during early development results in a significant hypomyelination of the mouse brain. Specifically, the brain of these animals presented a significant reduction of myelin proteins expression in combination with reduced numbers of myelinated axons. OPC development was also affected in these mice; the number of mature myelinating OLs was reduced as well as the proliferation and generation of new OPCs. These results indicate that the transferrin cycle, in which the transferrin receptor 1 is essential, is probably the main route of iron incorporation in OPCs during the postnatal development of the mouse brain."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The Role of Ferritin and Transferrin Receptor in Oligodendrocyte Maturation and Myelination"]}]}],"canonical_facts":{"dc:contributor":["Paez, Pablo","Pharmacology and Toxicology"],"dc:creator":["Wan, Rensheng"],"dc:date":["2019-10-28T19:53:09Z","2019","2019-05-29 11:20:05"],"dc:description":["M.S.","There is a critical relationship between oligodendrocyte (OL) development, myelin production and iron. Iron deficiency leads to hypomyelination both in humans and animal models, and the neurological sequelae of hypomyelination are significant. Therefore, understanding the molecular mechanisms of iron uptake and storage in OLs is necessary for planning effective strategies for iron supplementation. Ferritin is an intracellular protein that stores iron and releases it in a controlled fashion. Even though ferritin is highly express by oligodendrocyte progenitor cells (OPCs), nothing is known about the role of ferritin on OPC maturation and myelination. To determine whether ferritin is required for OPC maturation, we used the Cre-lox system to knock-out ferritin expression in vitro as well as in vivo. Blocking ferritin production reduce OPC iron uptake and significantly delay OPC development in primary cultures. In vivo, a significant hypomyelination was found in conditional knock-out mice in which ferritin was postnatally deleted in Sox10 positive OPCs. The brain of ferritin knock-out animals presented an important decrease in the expression levels of myelin proteins and a substantial reduction in the percentage of myelinated axons. This reduced postnatal myelination was accompanied by a significant decrease in the number of myelinating OLs and with a reduction in proliferating OPCs. These results indicate that ferritin is important for an appropriate OPC maturation and suggest that this iron storage protein is essential for the normal myelination of the mouse brain. We have also performed similar experiments in a conditional knock-out mouse in which the transferrin receptor 1 was deleted in OPCs. In this animals, the ablation of the transferrin receptor 1 in Sox10 positive OPCs during early development results in a significant hypomyelination of the mouse brain. Specifically, the brain of these animals presented a significant reduction of myelin proteins expression in combination with reduced numbers of myelinated axons. OPC development was also affected in these mice; the number of mature myelinating OLs was reduced as well as the proliferation and generation of new OPCs. These results indicate that the transferrin cycle, in which the transferrin receptor 1 is essential, is probably the main route of iron incorporation in OPCs during the postnatal development of the mouse brain."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/80609"],"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":["pharmacology"],"dc:title":["The Role of Ferritin and Transferrin Receptor in Oligodendrocyte Maturation and Myelination"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T19:05:23Z"}