Activation of lysophosphatidic acid receptor type 1 contributes to pathophysiology of spinal cord injury

et al.

Detalhes bibliográficos
Autores: Santos-Nogueira, Eva, Astudillo, Alma M., Balsinde, Jesús, López-Vales, Rubèn
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2015
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/157654
Acesso em linha:http://hdl.handle.net/10261/157654
Access Level:acceso abierto
Palavra-chave:Demyelination
Oligodendrocytes
Neuroprotection
Lysophosphatidic acid
Microglia
Spinal cord injury
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spelling Activation of lysophosphatidic acid receptor type 1 contributes to pathophysiology of spinal cord injurySantos-Nogueira, EvaAstudillo, Alma M.Balsinde, JesúsLópez-Vales, RubènDemyelinationOligodendrocytesNeuroprotectionLysophosphatidic acidMicrogliaSpinal cord injuryet al.Lysophosphatidic acid (LPA) is an extracellular lipid mediator involved in many physiological functions that signals through six known G-protein-coupled receptors (LPA1–LPA6). A wide range of LPA effects have been identified in the CNS, including neural progenitor cell physiology, astrocyte and microglia activation, neuronal cell death, axonal retraction, and development of neuropathic pain. However, little is known about the involvement of LPA in CNS pathologies. Herein, we demonstrate for the first time that LPA signaling via LPA1 contributes to secondary damage after spinal cord injury. LPA levels increase in the contused spinal cord parenchyma during the first 14 d. To model this potential contribution of LPA in the spinal cord, we injected LPA into the normal spinal cord, revealing that LPA induces microglia/macrophage activation and demyelination. Use of a selective LPA1 antagonist or mice lacking LPA1 linked receptor-mediated signaling to demyelination, which was in part mediated by microglia. Finally, we demonstrate that selective blockade of LPA1 after spinal cord injury results in reduced demyelination and improvement in locomotor recovery. Overall, these results support LPA–LPA1 signaling as a novel pathway that contributes to secondary damage after spinal cord contusion in mice and suggest that LPA1 antagonism might be useful for the treatment of acute spinal cord injury.This work was supported by National Institutes of Health Grant NS084398 (J.C.), Wings for Life Foundation, Marie-Curie International Reintegration Program Grant MC IRG 249274, Spanish Ministry of Economy and Competitiveness Grant SAF2013-48431-R, and the Health Research Fund of Spain [Cell Therapy Network and Center for Biomedical Research in Neurodegenerative Diseases Network (CIBERNED)] (R.L-V.) E.S.-N. is a recipient from a FPU fellowship.Peer ReviewedSociety for NeuroscienceNational Institutes of Health (US)Ministerio de Economía y Competitividad (España)MetLife FoundationInstituto de Salud Carlos IIIEuropean CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2017201720152017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/157654reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/FP7/249274info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-48431-Rhttps://doi.org/10.1523/JNEUROSCI.4703-14.2015Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1576542026-05-22T06:33:51Z
dc.title.none.fl_str_mv Activation of lysophosphatidic acid receptor type 1 contributes to pathophysiology of spinal cord injury
title Activation of lysophosphatidic acid receptor type 1 contributes to pathophysiology of spinal cord injury
spellingShingle Activation of lysophosphatidic acid receptor type 1 contributes to pathophysiology of spinal cord injury
Santos-Nogueira, Eva
Demyelination
Oligodendrocytes
Neuroprotection
Lysophosphatidic acid
Microglia
Spinal cord injury
title_short Activation of lysophosphatidic acid receptor type 1 contributes to pathophysiology of spinal cord injury
title_full Activation of lysophosphatidic acid receptor type 1 contributes to pathophysiology of spinal cord injury
title_fullStr Activation of lysophosphatidic acid receptor type 1 contributes to pathophysiology of spinal cord injury
title_full_unstemmed Activation of lysophosphatidic acid receptor type 1 contributes to pathophysiology of spinal cord injury
title_sort Activation of lysophosphatidic acid receptor type 1 contributes to pathophysiology of spinal cord injury
dc.creator.none.fl_str_mv Santos-Nogueira, Eva
Astudillo, Alma M.
Balsinde, Jesús
López-Vales, Rubèn
author Santos-Nogueira, Eva
author_facet Santos-Nogueira, Eva
Astudillo, Alma M.
Balsinde, Jesús
López-Vales, Rubèn
author_role author
author2 Astudillo, Alma M.
Balsinde, Jesús
López-Vales, Rubèn
author2_role author
author
author
dc.contributor.none.fl_str_mv National Institutes of Health (US)
Ministerio de Economía y Competitividad (España)
MetLife Foundation
Instituto de Salud Carlos III
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Demyelination
Oligodendrocytes
Neuroprotection
Lysophosphatidic acid
Microglia
Spinal cord injury
topic Demyelination
Oligodendrocytes
Neuroprotection
Lysophosphatidic acid
Microglia
Spinal cord injury
description et al.
publishDate 2015
dc.date.none.fl_str_mv 2015
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/157654
url http://hdl.handle.net/10261/157654
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/FP7/249274
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-48431-R
https://doi.org/10.1523/JNEUROSCI.4703-14.2015
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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