Activation of lysophosphatidic acid receptor type 1 (LPA1) contributes to pathophysiology of spinal cord injury
Santos Nogueira, Eva (Universitat Autònoma de Barcelona. Institut de Neurociències)
López-Serrano, Clara (Universitat Autònoma de Barcelona. Institut de Neurociències)
Hernández Martín, Joaquim (Universitat Autònoma de Barcelona. Institut de Neurociències)
Lago, Natalia (Institut Pasteur de Montevideo. Laboratorio de Neuroinflamación y Terapia Génica)
Astudillo, Alma M. (Consejo Superior de Investigaciones Científicas (Espanya). Instituto de Biología y Genética Molecular)
Balsinde, Jesús (Consejo Superior de Investigaciones Científicas (Espanya). Instituto de Biología y Genética Molecular)
Estivill-Torrus, Guillermo (Instituto de Investigación Biomédica de Málaga)
Rodríguez de Fonseca, Fernando (Instituto de Investigación Biomédica de Málaga)
Chun, Jerold (Scripps Research Institute. Dorris Neuroscience Center)
López Vales, Rubén (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date:	2015
Abstract:	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.
Grants:	European Commission 249274 Ministerio de Economía y Competitividad SAF2013-484
Note:	Altres ajuts: NIH/NS084398
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Demyelination ; Lysophosphatidic acid ; Microglia ; Neuroprotection ; Oligodendrocytes ; Spinal cord injury
Published in:	The Journal of neuroscience, Vol. 35, Num. 28 (2015) , p. 10224-10235, ISSN 1529-2401

DOI: 10.1523/JNEUROSCI.4703-14.2015
PMID: 26180199

12 p, 3.5 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles