Activation of lysophosphatidic acid receptor type 1 contributes to pathophysiology of spinal cord injury
| Autor: | Jesús Balsinde, Clara López-Serrano, Jerold Chun, Natalia Lago, Guillermo Estivill-Torrús, Fernando Rodríguez de Fonseca, Alma M. Astudillo, Eva Santos-Nogueira, Rubèn López-Vales, Joaquim Hernández |
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| Přispěvatelé: | National Institutes of Health (US), Ministerio de Economía y Competitividad (España), MetLife Foundation, Instituto de Salud Carlos III, European Commission, [Santos-Nogueira,E, López-Serrano,C, Hernández,J, López-Vales,R] Department of Cellular Biology, Physiology, and Immunology, Institute of Neurosciences, Center for Biomedical Research in Neurodegenerative Diseases Network (CIBERNED), Universitat Autónoma de Barcelona, Spain. [Lago,N] Neuroinflammation and Gene Therapy Laboratory, Pasteur Institute of Montevideo, Montevideo, Uruguay. [Astudillo,AM, Balsinde,J] Institute of Biology and Molecular Genetics, Spanish National Research Council, Valladolid, Spain. [Estivill-Torrús,G, Rodríguez de Fonseca,F] Research Laboratories, Interdepartmental Neuroscience and Mental Health Clinical Management Units, Institute for Biomedical Research of Málaga, Regional University Hospital of Málaga and Virgen de la Victoria, Málaga, Spain. [Chun,J] Molecular and Cellular Neuroscience Department, Dorris Neuroscience Center, Scripps Research Institute, La Jolla, California., 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.. We thank Bristol-Myers Squibb for the gift of AM095 |
| Rok vydání: | 2015 |
| Předmět: |
Time Factors
Organisms::Eukaryota::Animals::Animal Population Groups::Animals Newborn [Medical Subject Headings] Phenomena and Processes::Physical Phenomena::Time::Time Factors [Medical Subject Headings] Ratones transgénicos Receptores de ácidos lisofosfatídicos Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Membrane Proteins::Receptors Cell Surface::Receptors G-Protein-Coupled::Receptors Lysophospholipid::Receptors Lysophosphatidic Acid [Medical Subject Headings] traumatismos de la médula espinal chemistry.chemical_compound Mice Células cultivadas Lysophosphatidic acid Phenomena and Processes::Physiological Phenomena::Electrophysiological Phenomena::Evoked Potentials [Medical Subject Headings] Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity [Medical Subject Headings] Organisms::Eukaryota::Animals [Medical Subject Headings] Organisms::Eukaryota::Animals::Animal Population Groups::Animals Genetically Modified::Mice Transgenic [Medical Subject Headings] Receptors Lysophosphatidic Acid Spinal cord injury Cells Cultured Chemicals and Drugs::Lipids::Membrane Lipids::Phospholipids [Medical Subject Headings] Cerebral Cortex Microglia Cell Death Oligodendrocytes General Neuroscience Articles Neuroprotection Oligodendroglia medicine.anatomical_structure Potenciales evocados motores Spinal Cord Oligodendroglía Neuropathic pain Microglía Anatomy::Nervous System::Central Nervous System::Spinal Cord [Medical Subject Headings] Female lipids (amino acids peptides and proteins) biological phenomena cell phenomena and immunity Demyelination Microgria Astrocyte Diseases::Wounds and Injuries::Spinal Cord Injuries [Medical Subject Headings] Animales recién nacidos Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex [Medical Subject Headings] Mice Transgenic Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models Animal::Disease Models Animal [Medical Subject Headings] Motor Activity Médula espinal Lisofosfolípidos Anatomy::Cells::Neuroglia::Oligodendroglia [Medical Subject Headings] Ratas Diseases::Nervous System Diseases::Demyelinating Diseases [Medical Subject Headings] Modelos de enfermedad en animales ratones consanguíneos C57BL Corteza cerebral medicine Animals Anatomy::Cells::Neuroglia::Microglia [Medical Subject Headings] Spinal Cord Injuries Enfermedades desmielinizantes Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] business.industry Lipid signaling medicine.disease Spinal cord Evoked Potentials Motor Actividad motora Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death [Medical Subject Headings] Muerte celular Mice Inbred C57BL Disease Models Animal chemistry Animals Newborn Check Tags::Female [Medical Subject Headings] Anatomy::Cells::Cells Cultured [Medical Subject Headings] Factores de tiempo Lysophospholipids Organisms::Eukaryota::Animals::Animal Population Groups::Animals Laboratory::Animals Inbred Strains::Mice Inbred Strains::Mice Inbred C57BL [Medical Subject Headings] business Neuroscience Demyelinating Diseases |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 2013-4843 |
| Popis: | et 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. |
| Databáze: | OpenAIRE |
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