{"id":{"repo_id":"montana-tech","oai_identifier":"oai:scholarworks.umt.edu:etd-1596"},"canonical_url":"https://search.dev.ndltd.org/etd/montana-tech/oai:scholarworks.umt.edu:etd-1596","repository":{"repo_id":"montana-tech","name":"Montana Technology","base_url":"https://scholarworks.umt.edu/do/oai/"},"display":{"title":"Influence of Prion Protein Expression on Function of Excitatory Amino Acid Transporters in Mouse Primary Astrocytes","abstract":"Prion protein (PrP) is expressed on a wide variety of cells and plays an important role in the pathogenesis of transmissible spongiform encephalopathies. However, its normal function remains unclear. Mice that do not express PrP exhibit deficits in spatial memory and abnormalities in excitatory neurotransmission suggestive that PrP may function in the glutamatergic synapse. Here we show that transport of D-aspartate, a non-metabolized L-glutamate analog, through excitatory amino acid transporters (EAATs) was faster in astrocytes from PrP knockout (PrP KO) mice than in astrocytes from C57BL/10 SnJ wildtype (WT) mice. Experiments using EAAT subtype-specific inhibitors demonstrated that in both WT and PrP KO astrocytes, the majority of transport was mediated by EAAT1. Furthermore, PrP KO astrocytes were more effective than WT astrocytes at alleviating L-glutamate-mediated excitotoxic damage in both WT and PrP KO neuronal cultures. Thus, in this model, PrP KO astrocytes exerted a functional influence on neuronal survival and may therefore influence regulation of glutamatergic neurotransmission in vivo.","abstract_html":"Prion protein (PrP) is expressed on a wide variety of cells and plays an important role in the pathogenesis of transmissible spongiform encephalopathies. However, its normal function remains unclear. Mice that do not express PrP exhibit deficits in spatial memory and abnormalities in excitatory neurotransmission suggestive that PrP may function in the glutamatergic synapse. Here we show that transport of D-aspartate, a non-metabolized L-glutamate analog, through excitatory amino acid transporters (EAATs) was faster in astrocytes from PrP knockout (PrP KO) mice than in astrocytes from C57BL/10 SnJ wildtype (WT) mice. Experiments using EAAT subtype-specific inhibitors demonstrated that in both WT and PrP KO astrocytes, the majority of transport was mediated by EAAT1. Furthermore, PrP KO astrocytes were more effective than WT astrocytes at alleviating L-glutamate-mediated excitotoxic damage in both WT and PrP KO neuronal cultures. Thus, in this model, PrP KO astrocytes exerted a functional influence on neuronal survival and may therefore influence regulation of glutamatergic neurotransmission in vivo.","abstract_has_math":false,"creators":["Pathmajeyan, Melissa Selvy"],"institution":"University of Montana","degree_name":"Doctor of Philosophy (PhD)","degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-01-01T08:00:00Z","date_published":"2010-01-01T08:00:00Z","updated_at":"2026-07-24T03:13:28Z","subjects":["astrocytes","excitatory amino acid transporters","NMDA receptor","prion protein"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholarworks.umt.edu/etd/577","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Pathmajeyan, Melissa Selvy"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:publisher","label":"Institution","values":["University of Montana"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["astrocytes","excitatory amino acid transporters","NMDA receptor","prion protein"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarworks.umt.edu/etd/577"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Prion protein (PrP) is expressed on a wide variety of cells and plays an important role in the pathogenesis of transmissible spongiform encephalopathies. However, its normal function remains unclear. Mice that do not express PrP exhibit deficits in spatial memory and abnormalities in excitatory neurotransmission suggestive that PrP may function in the glutamatergic synapse. Here we show that transport of D-aspartate, a non-metabolized L-glutamate analog, through excitatory amino acid transporters (EAATs) was faster in astrocytes from PrP knockout (PrP KO) mice than in astrocytes from C57BL/10 SnJ wildtype (WT) mice. Experiments using EAAT subtype-specific inhibitors demonstrated that in both WT and PrP KO astrocytes, the majority of transport was mediated by EAAT1. Furthermore, PrP KO astrocytes were more effective than WT astrocytes at alleviating L-glutamate-mediated excitotoxic damage in both WT and PrP KO neuronal cultures. Thus, in this model, PrP KO astrocytes exerted a functional influence on neuronal survival and may therefore influence regulation of glutamatergic neurotransmission in vivo."]},{"key":"dc:title","label":"Title","values":["Influence of Prion Protein Expression on Function of Excitatory Amino Acid Transporters in Mouse Primary Astrocytes"]}]}],"canonical_facts":{"dc:creator":["Pathmajeyan, Melissa Selvy"],"dc:description.abstract":["Prion protein (PrP) is expressed on a wide variety of cells and plays an important role in the pathogenesis of transmissible spongiform encephalopathies. However, its normal function remains unclear. Mice that do not express PrP exhibit deficits in spatial memory and abnormalities in excitatory neurotransmission suggestive that PrP may function in the glutamatergic synapse. Here we show that transport of D-aspartate, a non-metabolized L-glutamate analog, through excitatory amino acid transporters (EAATs) was faster in astrocytes from PrP knockout (PrP KO) mice than in astrocytes from C57BL/10 SnJ wildtype (WT) mice. Experiments using EAAT subtype-specific inhibitors demonstrated that in both WT and PrP KO astrocytes, the majority of transport was mediated by EAAT1. Furthermore, PrP KO astrocytes were more effective than WT astrocytes at alleviating L-glutamate-mediated excitotoxic damage in both WT and PrP KO neuronal cultures. Thus, in this model, PrP KO astrocytes exerted a functional influence on neuronal survival and may therefore influence regulation of glutamatergic neurotransmission in vivo."],"dc:identifier":["https://scholarworks.umt.edu/etd/577"],"dc:publisher":["University of Montana"],"dc:subject":["astrocytes","excitatory amino acid transporters","NMDA receptor","prion protein"],"dc:title":["Influence of Prion Protein Expression on Function of Excitatory Amino Acid Transporters in Mouse Primary Astrocytes"],"dc:type":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T03:13:28Z"}