CB1 and LPA(1) Receptors Relationship in the Mouse Central Nervous System
dc.contributor.author | González de San Román, Estibaliz | |
dc.contributor.author | Manuel Vicente, Iván | |
dc.contributor.author | Ledent, Catherine | |
dc.contributor.author | Chun, Jerold | |
dc.contributor.author | Rodríguez de Fonseca, Fernando | |
dc.contributor.author | Estivill Torrús, Guillermo | |
dc.contributor.author | Santín Núñez, Luis Javier | |
dc.contributor.author | Rodríguez Puertas, Rafael | |
dc.date.accessioned | 2020-01-14T08:39:31Z | |
dc.date.available | 2020-01-14T08:39:31Z | |
dc.date.issued | 2019-09-19 | |
dc.identifier.citation | Frontiers In Molecular Neuroscience 12 : (2019) // Article ID 223 | es_ES |
dc.identifier.issn | 1662-5099 | |
dc.identifier.uri | http://hdl.handle.net/10810/38268 | |
dc.description.abstract | 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. | es_ES |
dc.description.sponsorship | 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. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Frontiers Media | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | neurolipids | es_ES |
dc.subject | lysophosphatidic acid | es_ES |
dc.subject | cannabinoids | es_ES |
dc.subject | GPCR | es_ES |
dc.subject | autoradiography | es_ES |
dc.subject | imaging mass spectrometry | es_ES |
dc.subject | brain | es_ES |
dc.subject | desorption/ionization mass-spectrometry | es_ES |
dc.subject | cannabinoid receptor | es_ES |
dc.subject | basolateral amygdala | es_ES |
dc.subject | n-acylethanolamines | es_ES |
dc.subject | lipid mediators | es_ES |
dc.subject | knockout mice | es_ES |
dc.subject | localization | es_ES |
dc.subject | maldi | es_ES |
dc.title | CB1 and LPA(1) Receptors Relationship in the Mouse Central Nervous System | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | 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. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.frontiersin.org/articles/10.3389/fnmol.2019.00223/full | es_ES |
dc.identifier.doi | 10.3389/fnmol.2019.00223 | |
dc.departamentoes | Farmacología | es_ES |
dc.departamentoeu | Farmakologia | es_ES |
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