{"id":{"repo_id":"okstate","oai_identifier":"oai:openresearch.okstate.edu:20.500.14446/344858"},"canonical_url":"https://search.dev.ndltd.org/etd/okstate/oai:openresearch.okstate.edu:20.500.14446/344858","repository":{"repo_id":"okstate","name":"Oklahoma State University","base_url":"https://openresearch.okstate.edu/server/oai/request"},"display":{"title":"Effects of β-funaltrexamine on lipopolysaccharide-induced inflammation and behavior","abstract":"Inflammation plays a crucial role in the development, progression, and severity of many prevalent systemic and neurological pathologies. A growing body of evidence has found that inflammation is a key aspect of cardiovascular disease, autoimmune disorders, cancer, neurodegenerative diseases, and neuropsychiatric conditions. Consequently, there is a critical need to develop targeted pharmaceuticals to mitigate systemic inflammation and inflammation-induced behavioral deficits. Our lab has previously demonstrated that acute β-FNA has selective anti-inflammatory effects in normal human astrocytes and reduces systemic inflammatory mediators and anxiety- and sickness-like behavior in male mice, predominantly through inhibition of p38 MAPK and NF-κB. The purpose of this study was to extend our knowledge of the cell-specific effects of acute β-FNA treatment using microglial cells, as well as study chronic pre-treatment effects on systemic inflammation and inflammation-induced behavioral deficits using a preclinical model. BV2 murine microglial cells were co-incubated with β-FNA and LPS at various times, while osmotic drug pumps were surgically inserted into mice that continually dispensed β-FNA for six days prior to LPS injection. Depressive-, anxiety-, and sickness-like behaviors were measured 24h after LPS injection, and then mice were terminated, and plasma, frontal cortex, hippocampus, and spleen tissues were harvested. CCL2, CXCL10, and IL-1β levels were measured in cell supernatant, CCL2 and CXCL10 were measured in frontal cortex, hippocampus, and spleen tissues, and IL-1β and corticosterone were measured in mouse plasma via ELISA. IDO1 and NLRP3 transcription were quantified via RT-qPCR from whole cell lysates and the afore-mentioned tissue homogenates. Additionally, p38 MAPK and STAT1 were quantified via Western blots in whole cell lysates. Acute β-FNA selectively reduced CCL2 and paradoxically potentiated LPS-driven IL-1β in BV2 cells, while exhibiting no effect on p38 MAPK, STAT1, NLRP3, or IDO1. Behavioral deficits were predominantly correlated with neuroinflammatory levels of CCL2, CXCL10, NLRP3, and IDO1. Additionally, chronic β-FNA pre-treatment greatly reduced systemic levels of CCL2 and CXCL10 and inhibited or abolished anxiety- and sickness-like behaviors. Interestingly, β-FNA increased frontal cortex inflammation and anxiety-like behavior under control conditions. Consequently, these studies provide additional insight into the actions and therapeutic potential of β-FNA and underscore areas that need further investigation.","abstract_html":"Inflammation plays a crucial role in the development, progression, and severity of many prevalent systemic and neurological pathologies. A growing body of evidence has found that inflammation is a key aspect of cardiovascular disease, autoimmune disorders, cancer, neurodegenerative diseases, and neuropsychiatric conditions. Consequently, there is a critical need to develop targeted pharmaceuticals to mitigate systemic inflammation and inflammation-induced behavioral deficits. Our lab has previously demonstrated that acute β-FNA has selective anti-inflammatory effects in normal human astrocytes and reduces systemic inflammatory mediators and anxiety- and sickness-like behavior in male mice, predominantly through inhibition of p38 MAPK and NF-κB. The purpose of this study was to extend our knowledge of the cell-specific effects of acute β-FNA treatment using microglial cells, as well as study chronic pre-treatment effects on systemic inflammation and inflammation-induced behavioral deficits using a preclinical model. BV2 murine microglial cells were co-incubated with β-FNA and LPS at various times, while osmotic drug pumps were surgically inserted into mice that continually dispensed β-FNA for six days prior to LPS injection. Depressive-, anxiety-, and sickness-like behaviors were measured 24h after LPS injection, and then mice were terminated, and plasma, frontal cortex, hippocampus, and spleen tissues were harvested. CCL2, CXCL10, and IL-1β levels were measured in cell supernatant, CCL2 and CXCL10 were measured in frontal cortex, hippocampus, and spleen tissues, and IL-1β and corticosterone were measured in mouse plasma via ELISA. IDO1 and NLRP3 transcription were quantified via RT-qPCR from whole cell lysates and the afore-mentioned tissue homogenates. Additionally, p38 MAPK and STAT1 were quantified via Western blots in whole cell lysates. Acute β-FNA selectively reduced CCL2 and paradoxically potentiated LPS-driven IL-1β in BV2 cells, while exhibiting no effect on p38 MAPK, STAT1, NLRP3, or IDO1. Behavioral deficits were predominantly correlated with neuroinflammatory levels of CCL2, CXCL10, NLRP3, and IDO1. Additionally, chronic β-FNA pre-treatment greatly reduced systemic levels of CCL2 and CXCL10 and inhibited or abolished anxiety- and sickness-like behaviors. Interestingly, β-FNA increased frontal cortex inflammation and anxiety-like behavior under control conditions. Consequently, these studies provide additional insight into the actions and therapeutic potential of β-FNA and underscore areas that need further investigation.","abstract_has_math":false,"creators":["Hodge, Karissa"],"institution":"Oklahoma State University","degree_name":null,"degree_level":null,"degree_discipline":"Biomedical Sciences","degree_department":null,"school":null,"contributors":[],"advisors":["Davis, Randall"],"committee_chairs":[],"committee_members":["Das, Subhas","Volberding, Jennifer","Arias, Hugo"],"year":2024,"date_issued":"2024-05","date_published":"2024-05","updated_at":"2026-07-24T03:37:50Z","subjects":[],"languages":["en_US"],"rights":["Copyright is held by the author who has granted the Oklahoma State University Library the non-exclusive right to share this material in its institutional repository. Contact Digital Library Services at lib-dls@okstate.edu or 405-744-9161 for the permission policy on the use, reproduction or distribution of this material."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14446/344858","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Davis, Randall"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Das, Subhas","Volberding, Jennifer","Arias, Hugo"]},{"key":"dc:creator","label":"Author","values":["Hodge, Karissa"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-07-18T19:10:54Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-07-18T19:10:54Z"]},{"key":"dc:date.issued","label":"Date","values":["2024-05"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Sciences"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Oklahoma State University"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en_US"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright is held by the author who has granted the Oklahoma State University Library the non-exclusive right to share this material in its institutional repository. Contact Digital Library Services at lib-dls@okstate.edu or 405-744-9161 for the permission policy on the use, reproduction or distribution of this material."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14446/344858"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Inflammation plays a crucial role in the development, progression, and severity of many prevalent systemic and neurological pathologies. A growing body of evidence has found that inflammation is a key aspect of cardiovascular disease, autoimmune disorders, cancer, neurodegenerative diseases, and neuropsychiatric conditions. Consequently, there is a critical need to develop targeted pharmaceuticals to mitigate systemic inflammation and inflammation-induced behavioral deficits. Our lab has previously demonstrated that acute β-FNA has selective anti-inflammatory effects in normal human astrocytes and reduces systemic inflammatory mediators and anxiety- and sickness-like behavior in male mice, predominantly through inhibition of p38 MAPK and NF-κB. The purpose of this study was to extend our knowledge of the cell-specific effects of acute β-FNA treatment using microglial cells, as well as study chronic pre-treatment effects on systemic inflammation and inflammation-induced behavioral deficits using a preclinical model. BV2 murine microglial cells were co-incubated with β-FNA and LPS at various times, while osmotic drug pumps were surgically inserted into mice that continually dispensed β-FNA for six days prior to LPS injection. Depressive-, anxiety-, and sickness-like behaviors were measured 24h after LPS injection, and then mice were terminated, and plasma, frontal cortex, hippocampus, and spleen tissues were harvested. CCL2, CXCL10, and IL-1β levels were measured in cell supernatant, CCL2 and CXCL10 were measured in frontal cortex, hippocampus, and spleen tissues, and IL-1β and corticosterone were measured in mouse plasma via ELISA. IDO1 and NLRP3 transcription were quantified via RT-qPCR from whole cell lysates and the afore-mentioned tissue homogenates. Additionally, p38 MAPK and STAT1 were quantified via Western blots in whole cell lysates. Acute β-FNA selectively reduced CCL2 and paradoxically potentiated LPS-driven IL-1β in BV2 cells, while exhibiting no effect on p38 MAPK, STAT1, NLRP3, or IDO1. Behavioral deficits were predominantly correlated with neuroinflammatory levels of CCL2, CXCL10, NLRP3, and IDO1. Additionally, chronic β-FNA pre-treatment greatly reduced systemic levels of CCL2 and CXCL10 and inhibited or abolished anxiety- and sickness-like behaviors. Interestingly, β-FNA increased frontal cortex inflammation and anxiety-like behavior under control conditions. Consequently, these studies provide additional insight into the actions and therapeutic potential of β-FNA and underscore areas that need further investigation."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Effects of β-funaltrexamine on lipopolysaccharide-induced inflammation and behavior"]}]}],"canonical_facts":{"dc:contributor.advisor":["Davis, Randall"],"dc:contributor.committeemember":["Das, Subhas","Volberding, Jennifer","Arias, Hugo"],"dc:creator":["Hodge, Karissa"],"dc:date.accessioned":["2024-07-18T19:10:54Z"],"dc:date.available":["2024-07-18T19:10:54Z"],"dc:date.issued":["2024-05"],"dc:description.abstract":["Inflammation plays a crucial role in the development, progression, and severity of many prevalent systemic and neurological pathologies. A growing body of evidence has found that inflammation is a key aspect of cardiovascular disease, autoimmune disorders, cancer, neurodegenerative diseases, and neuropsychiatric conditions. Consequently, there is a critical need to develop targeted pharmaceuticals to mitigate systemic inflammation and inflammation-induced behavioral deficits. Our lab has previously demonstrated that acute β-FNA has selective anti-inflammatory effects in normal human astrocytes and reduces systemic inflammatory mediators and anxiety- and sickness-like behavior in male mice, predominantly through inhibition of p38 MAPK and NF-κB. The purpose of this study was to extend our knowledge of the cell-specific effects of acute β-FNA treatment using microglial cells, as well as study chronic pre-treatment effects on systemic inflammation and inflammation-induced behavioral deficits using a preclinical model. BV2 murine microglial cells were co-incubated with β-FNA and LPS at various times, while osmotic drug pumps were surgically inserted into mice that continually dispensed β-FNA for six days prior to LPS injection. Depressive-, anxiety-, and sickness-like behaviors were measured 24h after LPS injection, and then mice were terminated, and plasma, frontal cortex, hippocampus, and spleen tissues were harvested. CCL2, CXCL10, and IL-1β levels were measured in cell supernatant, CCL2 and CXCL10 were measured in frontal cortex, hippocampus, and spleen tissues, and IL-1β and corticosterone were measured in mouse plasma via ELISA. IDO1 and NLRP3 transcription were quantified via RT-qPCR from whole cell lysates and the afore-mentioned tissue homogenates. Additionally, p38 MAPK and STAT1 were quantified via Western blots in whole cell lysates. Acute β-FNA selectively reduced CCL2 and paradoxically potentiated LPS-driven IL-1β in BV2 cells, while exhibiting no effect on p38 MAPK, STAT1, NLRP3, or IDO1. Behavioral deficits were predominantly correlated with neuroinflammatory levels of CCL2, CXCL10, NLRP3, and IDO1. Additionally, chronic β-FNA pre-treatment greatly reduced systemic levels of CCL2 and CXCL10 and inhibited or abolished anxiety- and sickness-like behaviors. Interestingly, β-FNA increased frontal cortex inflammation and anxiety-like behavior under control conditions. Consequently, these studies provide additional insight into the actions and therapeutic potential of β-FNA and underscore areas that need further investigation."],"dc:format":["application/pdf"],"dc:identifier.uri":["https://hdl.handle.net/20.500.14446/344858"],"dc:language":["en_US"],"dc:rights":["Copyright is held by the author who has granted the Oklahoma State University Library the non-exclusive right to share this material in its institutional repository. Contact Digital Library Services at lib-dls@okstate.edu or 405-744-9161 for the permission policy on the use, reproduction or distribution of this material."],"dc:title":["Effects of β-funaltrexamine on lipopolysaccharide-induced inflammation and behavior"],"thesis:degree_discipline":["Biomedical Sciences"],"thesis:institution_name":["Oklahoma State University"]},"updated_at":"2026-07-24T03:37:50Z"}