{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/79831"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/79831","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Voltage-Gated Calcium Channels Function in Reactive Astrocytes","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Zamora, Norma"],"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":"2019-07-29T15:27:53Z","date_published":"2019-07-29T15:27:53Z","updated_at":"2026-07-27T19:05:19Z","subjects":["neurosciences","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/10477/79831","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":["Zamora, Norma"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-07-29T15:27:53Z","2019","2019-05-24 10:02:05"]},{"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","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/10477/79831"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Astrocytes exhibit excitability in the form of intracellular Ca++ oscillations which are critical for the regulation of many cellular events (Cornell Bell et al., 1990). We previously reported that voltage-gated Ca++ channels, specifically the L-type Cav1.2 subunit, are centrally involved in triggering astrocyte reactivity in vitro (Cheli et al., 2016a). The mechanisms that govern astrocyte reactivity in vivo remain poorly understood. Thus, using the Cre-lox system we generated a Cav1.2 conditional knockout mouse to determine whether Cav1.2 Ca++ channels also contribute to astrocyte reactivity in vivo. This astrocytic Cav1.2 knockout mouse was tested in the cuprizone model of myelin injury and repair which causes astrocyte and microglia activation in the absence of a lymphocytic response (Matsushima and Morell, 2001). We have found that deletion of Cav1.2 channels in GFAP positive astrocytes during cuprizone-induced demyelination lead to a significant reduction in the degree of astrocyte and microglia activation and astrocyte proliferation. Furthermore, the production of pro-inflammatory factors such as TNFα, IL1β and TGFb1 was significantly decreased in Cav1.2 knockout mice. Our data indicate that this reduction in a proinflammatory environment is beneficial for the remyelination of the mouse brain. Similar results were found in mice treated with nimodipine; animals injected with nimodipine during the demyelination stage of the CPZ treatment displayed a reduction in astrocyte and microglial activation and proliferation as well as enhanced remyelination. Therefore, our results indicate that voltage-gated Ca++ channels play an essential role in the induction and proliferation of reactive astrocytes, and may be a viable target in pathological conditions where astrogliosis is apparent."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Voltage-Gated Calcium Channels Function in Reactive Astrocytes"]}]}],"canonical_facts":{"dc:contributor":["Paez, Pablo","Pharmacology and Toxicology"],"dc:creator":["Zamora, Norma"],"dc:date":["2019-07-29T15:27:53Z","2019","2019-05-24 10:02:05"],"dc:description":["Ph.D.","Astrocytes exhibit excitability in the form of intracellular Ca++ oscillations which are critical for the regulation of many cellular events (Cornell Bell et al., 1990). We previously reported that voltage-gated Ca++ channels, specifically the L-type Cav1.2 subunit, are centrally involved in triggering astrocyte reactivity in vitro (Cheli et al., 2016a). The mechanisms that govern astrocyte reactivity in vivo remain poorly understood. Thus, using the Cre-lox system we generated a Cav1.2 conditional knockout mouse to determine whether Cav1.2 Ca++ channels also contribute to astrocyte reactivity in vivo. This astrocytic Cav1.2 knockout mouse was tested in the cuprizone model of myelin injury and repair which causes astrocyte and microglia activation in the absence of a lymphocytic response (Matsushima and Morell, 2001). We have found that deletion of Cav1.2 channels in GFAP positive astrocytes during cuprizone-induced demyelination lead to a significant reduction in the degree of astrocyte and microglia activation and astrocyte proliferation. Furthermore, the production of pro-inflammatory factors such as TNFα, IL1β and TGFb1 was significantly decreased in Cav1.2 knockout mice. Our data indicate that this reduction in a proinflammatory environment is beneficial for the remyelination of the mouse brain. Similar results were found in mice treated with nimodipine; animals injected with nimodipine during the demyelination stage of the CPZ treatment displayed a reduction in astrocyte and microglial activation and proliferation as well as enhanced remyelination. Therefore, our results indicate that voltage-gated Ca++ channels play an essential role in the induction and proliferation of reactive astrocytes, and may be a viable target in pathological conditions where astrogliosis is apparent."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/79831"],"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","pharmacology"],"dc:title":["Voltage-Gated Calcium Channels Function in Reactive Astrocytes"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:19Z"}