CB1 and LPA(1) Receptors Relationship in the Mouse Central Nervous System

Neurolipids are a class of bioactive lipids that are produced locally through specific biosynthetic pathways in response to extracellular stimuli. Neurolipids are important endogenous regulators of neural cell proliferation, differentiation, oxidative stress, inflammation and apoptosis. Endocannabin...

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Autores: González de San Román, Estibaliz, Manuel Vicente, Iván, Ledent, Catherine, Chun, Jerold, Rodríguez de Fonseca, Fernando, Estivill Torrús, Guillermo, Santín Núñez, Luis Javier, Rodríguez Puertas, Rafael
Tipo de documento: artigo
Data de publicação:2019
País:España
Recursos:Universidad del País Vasco
Repositório:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/38268
Acesso em linha:http://hdl.handle.net/10810/38268
Access Level:Acceso aberto
Palavra-chave:neurolipids
lysophosphatidic acid
cannabinoids
GPCR
autoradiography
imaging mass spectrometry
brain
desorption/ionization mass-spectrometry
cannabinoid receptor
basolateral amygdala
n-acylethanolamines
lipid mediators
knockout mice
localization
maldi
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repository_id_str
spelling CB1 and LPA(1) Receptors Relationship in the Mouse Central Nervous SystemGonzález de San Román, EstibalizManuel Vicente, IvánLedent, CatherineChun, JeroldRodríguez de Fonseca, FernandoEstivill Torrús, GuillermoSantín Núñez, Luis JavierRodríguez Puertas, Rafaelneurolipidslysophosphatidic acidcannabinoidsGPCRautoradiographyimaging mass spectrometrybraindesorption/ionization mass-spectrometrycannabinoid receptorbasolateral amygdalan-acylethanolamineslipid mediatorsknockout micelocalizationmaldiNeurolipids are a class of bioactive lipids that are produced locally through specific biosynthetic pathways in response to extracellular stimuli. Neurolipids are important endogenous regulators of neural cell proliferation, differentiation, oxidative stress, inflammation and apoptosis. Endocannabinoids (eCBs) and lysophosphatidic acid (LPA) are examples of this type of molecule and are involved in neuroprotection. The present study analyzes a possible relationship of the main receptor subtypes for both neurolipid systems that are present in the central nervous system, the CB1 and LPA(1) receptors, by using brain slices from CB1 KO mice and LPA(1)-null mice. Receptor-mediated G protein activation and glycerophospholipid regulation of potential precursors of their endogenous neurotransmitters were measured by two different in vitro imaging techniques, functional autoradiography and imaging mass spectrometry (IMS), respectively. Possible crosstalk between CB1 and LPA(1) receptors was identified in specific areas of the brain, such as the amygdala, where LPA(1) receptor activity is upregulated in CB1 KO mice. More evidence of an interaction between both systems was that the CB1-mediated activity was clearly increased in the prefrontal cortex and cerebellum of LPA(1)-null mice. The eCB system was specifically over-activated in regions where LPA(1) has an important signaling role during embryonic development. The modifications on phospholipids (PLs) observed in these genetically modified mice by using the IMS technique indicated the regulation of some of the PL precursors of both LPA and eCBs in specific brain areas. For example, phosphatidylcholine (PC) (36:1) was detected as a potential LPA precursor, and phosphatidylethanolamine (PE) (40:6) and PE (p18:0/22:6) as potential eCB precursors. The absence of the main cerebral receptors for LPA or eCB systems is able to induce modulation on the other at the levels of both signaling and synthesis of endogenous neurotransmitters, indicating adaptive responses between both systems during prenatal and/or postnatal development.This work was supported by the Departments of Industry and Education from the Basque Government KK-2017/14 Elkartek and IT975-16 Consolidated Research Group Grants. Technical and human support provided by the General Research Services SGIker [University of the Basque Country (UPV/EHU), Ministry of Economy and Competitiveness (MINECO), Basque Government, European Regional Development Fund (ERDF) and European Social Fund (ESF)] is gratefully acknowledged.Frontiers Media202020202019info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/38268reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.frontiersin.org/articles/10.3389/fnmol.2019.00223/fullinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/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.Atribución 3.0 Españaoai:addi.ehu.eus:10810/382682026-06-18T09:23:17Z
dc.title.none.fl_str_mv CB1 and LPA(1) Receptors Relationship in the Mouse Central Nervous System
title CB1 and LPA(1) Receptors Relationship in the Mouse Central Nervous System
spellingShingle CB1 and LPA(1) Receptors Relationship in the Mouse Central Nervous System
González de San Román, Estibaliz
neurolipids
lysophosphatidic acid
cannabinoids
GPCR
autoradiography
imaging mass spectrometry
brain
desorption/ionization mass-spectrometry
cannabinoid receptor
basolateral amygdala
n-acylethanolamines
lipid mediators
knockout mice
localization
maldi
title_short CB1 and LPA(1) Receptors Relationship in the Mouse Central Nervous System
title_full CB1 and LPA(1) Receptors Relationship in the Mouse Central Nervous System
title_fullStr CB1 and LPA(1) Receptors Relationship in the Mouse Central Nervous System
title_full_unstemmed CB1 and LPA(1) Receptors Relationship in the Mouse Central Nervous System
title_sort CB1 and LPA(1) Receptors Relationship in the Mouse Central Nervous System
dc.creator.none.fl_str_mv González de San Román, Estibaliz
Manuel Vicente, Iván
Ledent, Catherine
Chun, Jerold
Rodríguez de Fonseca, Fernando
Estivill Torrús, Guillermo
Santín Núñez, Luis Javier
Rodríguez Puertas, Rafael
author González de San Román, Estibaliz
author_facet González de San Román, Estibaliz
Manuel Vicente, Iván
Ledent, Catherine
Chun, Jerold
Rodríguez de Fonseca, Fernando
Estivill Torrús, Guillermo
Santín Núñez, Luis Javier
Rodríguez Puertas, Rafael
author_role author
author2 Manuel Vicente, Iván
Ledent, Catherine
Chun, Jerold
Rodríguez de Fonseca, Fernando
Estivill Torrús, Guillermo
Santín Núñez, Luis Javier
Rodríguez Puertas, Rafael
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv neurolipids
lysophosphatidic acid
cannabinoids
GPCR
autoradiography
imaging mass spectrometry
brain
desorption/ionization mass-spectrometry
cannabinoid receptor
basolateral amygdala
n-acylethanolamines
lipid mediators
knockout mice
localization
maldi
topic neurolipids
lysophosphatidic acid
cannabinoids
GPCR
autoradiography
imaging mass spectrometry
brain
desorption/ionization mass-spectrometry
cannabinoid receptor
basolateral amygdala
n-acylethanolamines
lipid mediators
knockout mice
localization
maldi
description Neurolipids are a class of bioactive lipids that are produced locally through specific biosynthetic pathways in response to extracellular stimuli. Neurolipids are important endogenous regulators of neural cell proliferation, differentiation, oxidative stress, inflammation and apoptosis. Endocannabinoids (eCBs) and lysophosphatidic acid (LPA) are examples of this type of molecule and are involved in neuroprotection. The present study analyzes a possible relationship of the main receptor subtypes for both neurolipid systems that are present in the central nervous system, the CB1 and LPA(1) receptors, by using brain slices from CB1 KO mice and LPA(1)-null mice. Receptor-mediated G protein activation and glycerophospholipid regulation of potential precursors of their endogenous neurotransmitters were measured by two different in vitro imaging techniques, functional autoradiography and imaging mass spectrometry (IMS), respectively. Possible crosstalk between CB1 and LPA(1) receptors was identified in specific areas of the brain, such as the amygdala, where LPA(1) receptor activity is upregulated in CB1 KO mice. More evidence of an interaction between both systems was that the CB1-mediated activity was clearly increased in the prefrontal cortex and cerebellum of LPA(1)-null mice. The eCB system was specifically over-activated in regions where LPA(1) has an important signaling role during embryonic development. The modifications on phospholipids (PLs) observed in these genetically modified mice by using the IMS technique indicated the regulation of some of the PL precursors of both LPA and eCBs in specific brain areas. For example, phosphatidylcholine (PC) (36:1) was detected as a potential LPA precursor, and phosphatidylethanolamine (PE) (40:6) and PE (p18:0/22:6) as potential eCB precursors. The absence of the main cerebral receptors for LPA or eCB systems is able to induce modulation on the other at the levels of both signaling and synthesis of endogenous neurotransmitters, indicating adaptive responses between both systems during prenatal and/or postnatal development.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/38268
url http://hdl.handle.net/10810/38268
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.frontiersin.org/articles/10.3389/fnmol.2019.00223/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
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 15.300724

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