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Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ(9)-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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491684/
https://www.ncbi.nlm.nih.gov/pubmed/31068789
http://dx.doi.org/10.3389/fnmol.2019.00096
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author 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_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_sort Silva-Peña, Daniel
collection PubMed
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 Δ(9)-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.
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spelling pubmed-64916842019-05-08 Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ(9)-THC and Ethanol Binge Drinking During Adolescence 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 Front Mol Neurosci Neuroscience 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 Δ(9)-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. Frontiers Media S.A. 2019-04-24 /pmc/articles/PMC6491684/ /pubmed/31068789 http://dx.doi.org/10.3389/fnmol.2019.00096 Text en Copyright © 2019 Silva-Peña, Rivera, Alén, Vargas, Rubio, García-Marchena, Pavón, Serrano, Rodríguez de Fonseca and Suárez. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
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
Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ(9)-THC and Ethanol Binge Drinking During Adolescence
title Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ(9)-THC and Ethanol Binge Drinking During Adolescence
title_full Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ(9)-THC and Ethanol Binge Drinking During Adolescence
title_fullStr Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ(9)-THC and Ethanol Binge Drinking During Adolescence
title_full_unstemmed Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ(9)-THC and Ethanol Binge Drinking During Adolescence
title_short Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ(9)-THC and Ethanol Binge Drinking During Adolescence
title_sort oleoylethanolamide modulates bdnf-erk signaling and neurogenesis in the hippocampi of rats exposed to δ(9)-thc and ethanol binge drinking during adolescence
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491684/
https://www.ncbi.nlm.nih.gov/pubmed/31068789
http://dx.doi.org/10.3389/fnmol.2019.00096
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