Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ9-THC and Ethanol Binge Drinking During Adolescence.
Oleoylethanolamide is an endogenous NAE that modulates ethanol-seeking behavior and ethanol-induced neuroinflammation. In the present study we further analyze the role of OEA in hippocampal neurogenesis, BDNF-ERK signaling, and spatial memory that are affected by alcohol. Additionally, we addressed...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/17856 |
| Acceso en línea: | http://hdl.handle.net/20.500.12105/17856 |
| Access Level: | acceso abierto |
| Palabra clave: | ERK Alcohol Brain-derived neurotrophic factor Hippocampus Memory Oleoylethanolamide |
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Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ9-THC and Ethanol Binge Drinking During Adolescence.Silva-Peña, DanielRivera, PatriciaAlén, FranciscoVargas, AntonioRubio, LeticiaGarcía-Marchena, NuriaPavón, Francisco JavierSerrano, AntoniaRodríguez de Fonseca, FernandoSuárez, JuanERKAlcoholBrain-derived neurotrophic factorHippocampusMemoryOleoylethanolamideOleoylethanolamide is an endogenous NAE that modulates ethanol-seeking behavior and ethanol-induced neuroinflammation. In the present study we further analyze the role of OEA in hippocampal neurogenesis, BDNF-ERK signaling, and spatial memory that are affected by alcohol. Additionally, we addressed the effects of OEA on the association of alcohol and cannabis, a frequent combination in human alcohol addicts, and whose long-term effects are far from being understood. To this end, OEA (10 mg/kg/day, i.p.) was pharmacologically administered for 5 days/week in a preclinical model of adolescent rats with binge-like consumption (1 day/week) of ethanol (3 g/kg, i.g.) combined or not with acute administrations of Δ9-THC (5 mg/kg, i.p.) for 5 weeks. OEA restored ethanol/THC-related decreases in both short-term spatial memory (spontaneous alternation by Y-maze) and circulating levels of BDNF, reduced cell proliferation (Mki67 and IdU+ cells) and maturation (Dcx, Calb1), and improved cell survival (Casp3 and BrdU+ cells) in the dorsal hippocampus. Interestingly, OEA alone or combined with THC also decreased the mRNA levels of neurotrophic factors (Bdnf, Ntf3) and the NT3 receptor TrkC, but increased the BDNF receptor TrkB in the hippocampus of ethanol-exposed rats. These effects were likely associated with a OEA-specific phosphorylation of AKT and ERK1, key signaling regulators of cell proliferation and survival. These results suggest a regulatory role of OEA in short-term spatial memory and hippocampal neurogenesis through BDNF/AKT/ERK1 signaling in response to acute THC in an alcoholic context during adolescence.20242024-02-1020192019-04-2420192019-04-24research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.12105/17856reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/178562026-06-12T12:43:37Z |
| dc.title.none.fl_str_mv |
Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ9-THC and Ethanol Binge Drinking During Adolescence. |
| title |
Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ9-THC and Ethanol Binge Drinking During Adolescence. |
| spellingShingle |
Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ9-THC and Ethanol Binge Drinking During Adolescence. Silva-Peña, Daniel ERK Alcohol Brain-derived neurotrophic factor Hippocampus Memory Oleoylethanolamide |
| title_short |
Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ9-THC and Ethanol Binge Drinking During Adolescence. |
| title_full |
Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ9-THC and Ethanol Binge Drinking During Adolescence. |
| title_fullStr |
Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ9-THC and Ethanol Binge Drinking During Adolescence. |
| title_full_unstemmed |
Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ9-THC and Ethanol Binge Drinking During Adolescence. |
| title_sort |
Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ9-THC and Ethanol Binge Drinking During Adolescence. |
| dc.creator.none.fl_str_mv |
Silva-Peña, Daniel Rivera, Patricia Alén, Francisco Vargas, Antonio Rubio, Leticia García-Marchena, Nuria Pavón, Francisco Javier Serrano, Antonia Rodríguez de Fonseca, Fernando Suárez, Juan |
| author |
Silva-Peña, Daniel |
| author_facet |
Silva-Peña, Daniel Rivera, Patricia Alén, Francisco Vargas, Antonio Rubio, Leticia García-Marchena, Nuria Pavón, Francisco Javier Serrano, Antonia Rodríguez de Fonseca, Fernando Suárez, Juan |
| author_role |
author |
| author2 |
Rivera, Patricia Alén, Francisco Vargas, Antonio Rubio, Leticia García-Marchena, Nuria Pavón, Francisco Javier Serrano, Antonia Rodríguez de Fonseca, Fernando Suárez, Juan |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
|
| dc.subject.none.fl_str_mv |
ERK Alcohol Brain-derived neurotrophic factor Hippocampus Memory Oleoylethanolamide |
| topic |
ERK Alcohol Brain-derived neurotrophic factor Hippocampus Memory Oleoylethanolamide |
| description |
Oleoylethanolamide is an endogenous NAE that modulates ethanol-seeking behavior and ethanol-induced neuroinflammation. In the present study we further analyze the role of OEA in hippocampal neurogenesis, BDNF-ERK signaling, and spatial memory that are affected by alcohol. Additionally, we addressed the effects of OEA on the association of alcohol and cannabis, a frequent combination in human alcohol addicts, and whose long-term effects are far from being understood. To this end, OEA (10 mg/kg/day, i.p.) was pharmacologically administered for 5 days/week in a preclinical model of adolescent rats with binge-like consumption (1 day/week) of ethanol (3 g/kg, i.g.) combined or not with acute administrations of Δ9-THC (5 mg/kg, i.p.) for 5 weeks. OEA restored ethanol/THC-related decreases in both short-term spatial memory (spontaneous alternation by Y-maze) and circulating levels of BDNF, reduced cell proliferation (Mki67 and IdU+ cells) and maturation (Dcx, Calb1), and improved cell survival (Casp3 and BrdU+ cells) in the dorsal hippocampus. Interestingly, OEA alone or combined with THC also decreased the mRNA levels of neurotrophic factors (Bdnf, Ntf3) and the NT3 receptor TrkC, but increased the BDNF receptor TrkB in the hippocampus of ethanol-exposed rats. These effects were likely associated with a OEA-specific phosphorylation of AKT and ERK1, key signaling regulators of cell proliferation and survival. These results suggest a regulatory role of OEA in short-term spatial memory and hippocampal neurogenesis through BDNF/AKT/ERK1 signaling in response to acute THC in an alcoholic context during adolescence. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2019-04-24 2019 2019-04-24 2024 2024-02-10 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/20.500.12105/17856 |
| url |
http://hdl.handle.net/20.500.12105/17856 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.source.none.fl_str_mv |
reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII) |
| instname_str |
Instituto de Salud Carlos III (ISCIII) |
| reponame_str |
Repisalud |
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Repisalud |
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|
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|
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1869422178608349185 |
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15,811543 |