{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/86798"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/86798","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Iron Metabolism in Astrocytes, Implications for Oligodendrocyte Maturation and Myelination","abstract":"M.S.","abstract_html":"M.S.","abstract_has_math":false,"creators":["Wan, Qiuchen"],"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":2025,"date_issued":"2025-02-25T23:22:52Z","date_published":"2025-02-25T23:22:52Z","updated_at":"2026-07-27T19:05:37Z","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/10477/86798","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, Qiuchen"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-02-25T23:22:52Z","2020","2020-06-25 21:15:36"]},{"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/10477/86798"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["M.S.","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 homeostasis in oligodendrocytes is necessary for planning effective strategies for iron supplementation. Astrocytes are the most abundant glial cells in the brain, and are the only cells in close contact with blood vessels. Therefore, they are strategically located to acquire nutrients from the circulating blood such as iron. We have found that iron incorporation and storage by astrocytes is essential for the normal development of oligodendrocytes progenitor cells (OPCs) as well as for the postnatal myelination of the mouse Central Nervous System (CNS). We used the Cre-lox system to knock-out the ferritin heavy subunit (Fth), the transferrin receptor 1 (Tfr1) and the divalent metal transporter 1 (DMT1) expression in Glast-1 positive astrocytes. Blocking Fth or DMT1 production specifically in astrocytes reduce oligodendrocyte iron uptake and significantly delay OPC development in the postnatal brain. Furthermore, a significant hypomyelination was found in these two conditional knockout mice. The brain of Fth and DMT1 knockout 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 total number of oligodendrocytes and in the density of myelinating glia. On the other hand, the ablation of the Tfr1 in astrocytes do not significantly affects the development of new oligodendrocytes or their iron homeostasis. These results indicate that Fth and DMT1 are important molecules for astrocyte iron incorporation and storage and suggest that a normal iron metabolism in astrocytes is essential for OPC development and for the myelination of the mouse brain.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Iron Metabolism in Astrocytes, Implications for Oligodendrocyte Maturation and Myelination"]}]}],"canonical_facts":{"dc:contributor":["Paez, Pablo","Pharmacology and Toxicology"],"dc:creator":["Wan, Qiuchen"],"dc:date":["2025-02-25T23:22:52Z","2020","2020-06-25 21:15:36"],"dc:description":["M.S.","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 homeostasis in oligodendrocytes is necessary for planning effective strategies for iron supplementation. Astrocytes are the most abundant glial cells in the brain, and are the only cells in close contact with blood vessels. Therefore, they are strategically located to acquire nutrients from the circulating blood such as iron. We have found that iron incorporation and storage by astrocytes is essential for the normal development of oligodendrocytes progenitor cells (OPCs) as well as for the postnatal myelination of the mouse Central Nervous System (CNS). We used the Cre-lox system to knock-out the ferritin heavy subunit (Fth), the transferrin receptor 1 (Tfr1) and the divalent metal transporter 1 (DMT1) expression in Glast-1 positive astrocytes. Blocking Fth or DMT1 production specifically in astrocytes reduce oligodendrocyte iron uptake and significantly delay OPC development in the postnatal brain. Furthermore, a significant hypomyelination was found in these two conditional knockout mice. The brain of Fth and DMT1 knockout 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 total number of oligodendrocytes and in the density of myelinating glia. On the other hand, the ablation of the Tfr1 in astrocytes do not significantly affects the development of new oligodendrocytes or their iron homeostasis. These results indicate that Fth and DMT1 are important molecules for astrocyte iron incorporation and storage and suggest that a normal iron metabolism in astrocytes is essential for OPC development and for the myelination of the mouse brain.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/86798"],"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":["Iron Metabolism in Astrocytes, Implications for Oligodendrocyte Maturation and Myelination"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T19:05:37Z"}