Up-regulation of CB1 Cannabinoid Receptors Located at Glutamatergic Terminals in the Medial Prefrontal Cortex of the Obese Zucker Rat.

The present study describes a detailed neuroanatomical distribution map of the cannabinoid type 1 (CB1) receptor, along with the biochemical characterization of the expression and functional coupling to their cognate G i/o proteins in the medial prefrontal cortex (mPCx) of the obese Zucker rats. The...

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Authors: Echeazarra Escudero, Leyre, Barrondo Lacarra, Sergio, García del Caño, Gontzal, Bonilla del Río, Itziar, Egaña Huguet, Jon, Puente Bustinza, Nagore, Aretxabala Rodríguez, Xabier, Montaña, Mario, López de Jesús, Maider, González Burguera, Imanol, Saumell Esnaola, Miquel, Goicolea Altuna, María Aranzazu, Grandes Moreno, Pedro Rolando, Sallés Alvira, Joan
Format: article
Publication Date:2022
Country:España
Institution:Universidad del País Vasco
Repository:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/65200
Online Access:http://hdl.handle.net/10810/65200
Access Level:Open access
Keyword:2-AG levels
CB1 receptor
Gi/o proteins
excitatory synapses
glutamatergic terminals
long-term potentiation
medial prefrontal cortex
obese Zucker rat
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spelling Up-regulation of CB1 Cannabinoid Receptors Located at Glutamatergic Terminals in the Medial Prefrontal Cortex of the Obese Zucker Rat.Echeazarra Escudero, LeyreBarrondo Lacarra, SergioGarcía del Caño, GontzalBonilla del Río, ItziarEgaña Huguet, JonPuente Bustinza, NagoreAretxabala Rodríguez, XabierMontaña, MarioLópez de Jesús, MaiderGonzález Burguera, ImanolSaumell Esnaola, MiquelGoicolea Altuna, María AranzazuGrandes Moreno, Pedro RolandoSallés Alvira, Joan2-AG levelsCB1 receptorGi/o proteinsexcitatory synapsesglutamatergic terminalslong-term potentiationmedial prefrontal cortexobese Zucker ratThe present study describes a detailed neuroanatomical distribution map of the cannabinoid type 1 (CB1) receptor, along with the biochemical characterization of the expression and functional coupling to their cognate G i/o proteins in the medial prefrontal cortex (mPCx) of the obese Zucker rats. The CB1 receptor density was higher in the prelimbic (PL) and infralimbic (IL) subregions of the mPCx of obese Zucker rats relative to their lean littermates which was associated with a higher percentage of CB1 receptor immunopositive excitatory presynaptic terminals in PL and IL. Also, a higher expression of CB1 receptors and WIN55,212-2-stimulated [35S]GTPγS binding was observed in the mPCx but not in the neocortex (NCx) and hippocampus of obese rats. Low-frequency stimulation in layers II/III of the mPCx induced CB1 receptor-dependent long-term synaptic plasticity in IL of area obese Zucker but not lean rats. Overall, the elevated 2-AG levels, up-regulation of CB1 receptors, and increased agonist-stimulated [35S]GTPγS binding strongly suggest that hyperactivity of the endocannabinoid signaling takes place at the glutamatergic terminals of the mPCx in the obese Zucker rat. These findings could endorse the importance of the CB1 receptors located in the mPCx in the development of obesity in Zucker rats.This work was supported by grants of the Basque Government (grants numbers IT1230-19 and IT1620-22 to PG), the Spanish Government (grant numbers CTQ2017-85686-R to MG and JS) and the Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Frontiers Media202420242022info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/65200reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MINECO/CTQ2017-85686-R/https://www.frontiersin.org/articles/10.3389/fnana.2022.1004702/fullinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/Copyright © 2022 Echeazarra, Barrondo, García del Caño, Bonilla-Del Río, Egaña-Huguet, Puente, Aretxabala, Montaña, López de Jesús, González-Burguera, Saumell-Esnaola, Goicolea, Grandes and Sallés. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)oai:addi.ehu.eus:10810/652002026-06-18T09:23:17Z
dc.title.none.fl_str_mv Up-regulation of CB1 Cannabinoid Receptors Located at Glutamatergic Terminals in the Medial Prefrontal Cortex of the Obese Zucker Rat.
title Up-regulation of CB1 Cannabinoid Receptors Located at Glutamatergic Terminals in the Medial Prefrontal Cortex of the Obese Zucker Rat.
spellingShingle Up-regulation of CB1 Cannabinoid Receptors Located at Glutamatergic Terminals in the Medial Prefrontal Cortex of the Obese Zucker Rat.
Echeazarra Escudero, Leyre
2-AG levels
CB1 receptor
Gi/o proteins
excitatory synapses
glutamatergic terminals
long-term potentiation
medial prefrontal cortex
obese Zucker rat
title_short Up-regulation of CB1 Cannabinoid Receptors Located at Glutamatergic Terminals in the Medial Prefrontal Cortex of the Obese Zucker Rat.
title_full Up-regulation of CB1 Cannabinoid Receptors Located at Glutamatergic Terminals in the Medial Prefrontal Cortex of the Obese Zucker Rat.
title_fullStr Up-regulation of CB1 Cannabinoid Receptors Located at Glutamatergic Terminals in the Medial Prefrontal Cortex of the Obese Zucker Rat.
title_full_unstemmed Up-regulation of CB1 Cannabinoid Receptors Located at Glutamatergic Terminals in the Medial Prefrontal Cortex of the Obese Zucker Rat.
title_sort Up-regulation of CB1 Cannabinoid Receptors Located at Glutamatergic Terminals in the Medial Prefrontal Cortex of the Obese Zucker Rat.
dc.creator.none.fl_str_mv Echeazarra Escudero, Leyre
Barrondo Lacarra, Sergio
García del Caño, Gontzal
Bonilla del Río, Itziar
Egaña Huguet, Jon
Puente Bustinza, Nagore
Aretxabala Rodríguez, Xabier
Montaña, Mario
López de Jesús, Maider
González Burguera, Imanol
Saumell Esnaola, Miquel
Goicolea Altuna, María Aranzazu
Grandes Moreno, Pedro Rolando
Sallés Alvira, Joan
author Echeazarra Escudero, Leyre
author_facet Echeazarra Escudero, Leyre
Barrondo Lacarra, Sergio
García del Caño, Gontzal
Bonilla del Río, Itziar
Egaña Huguet, Jon
Puente Bustinza, Nagore
Aretxabala Rodríguez, Xabier
Montaña, Mario
López de Jesús, Maider
González Burguera, Imanol
Saumell Esnaola, Miquel
Goicolea Altuna, María Aranzazu
Grandes Moreno, Pedro Rolando
Sallés Alvira, Joan
author_role author
author2 Barrondo Lacarra, Sergio
García del Caño, Gontzal
Bonilla del Río, Itziar
Egaña Huguet, Jon
Puente Bustinza, Nagore
Aretxabala Rodríguez, Xabier
Montaña, Mario
López de Jesús, Maider
González Burguera, Imanol
Saumell Esnaola, Miquel
Goicolea Altuna, María Aranzazu
Grandes Moreno, Pedro Rolando
Sallés Alvira, Joan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv 2-AG levels
CB1 receptor
Gi/o proteins
excitatory synapses
glutamatergic terminals
long-term potentiation
medial prefrontal cortex
obese Zucker rat
topic 2-AG levels
CB1 receptor
Gi/o proteins
excitatory synapses
glutamatergic terminals
long-term potentiation
medial prefrontal cortex
obese Zucker rat
description The present study describes a detailed neuroanatomical distribution map of the cannabinoid type 1 (CB1) receptor, along with the biochemical characterization of the expression and functional coupling to their cognate G i/o proteins in the medial prefrontal cortex (mPCx) of the obese Zucker rats. The CB1 receptor density was higher in the prelimbic (PL) and infralimbic (IL) subregions of the mPCx of obese Zucker rats relative to their lean littermates which was associated with a higher percentage of CB1 receptor immunopositive excitatory presynaptic terminals in PL and IL. Also, a higher expression of CB1 receptors and WIN55,212-2-stimulated [35S]GTPγS binding was observed in the mPCx but not in the neocortex (NCx) and hippocampus of obese rats. Low-frequency stimulation in layers II/III of the mPCx induced CB1 receptor-dependent long-term synaptic plasticity in IL of area obese Zucker but not lean rats. Overall, the elevated 2-AG levels, up-regulation of CB1 receptors, and increased agonist-stimulated [35S]GTPγS binding strongly suggest that hyperactivity of the endocannabinoid signaling takes place at the glutamatergic terminals of the mPCx in the obese Zucker rat. These findings could endorse the importance of the CB1 receptors located in the mPCx in the development of obesity in Zucker rats.
publishDate 2022
dc.date.none.fl_str_mv 2022
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/65200
url http://hdl.handle.net/10810/65200
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO/CTQ2017-85686-R/
https://www.frontiersin.org/articles/10.3389/fnana.2022.1004702/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/es/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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