RT Journal Article
T1 Activation of Lysophosphatidic Acid Receptor Type 1 Contributes to Pathophysiology of Spinal Cord Injury.
A1 Santos-Nogueira, Eva
A1 López-Serrano, Clara
A1 Hernández, Joaquim
A1 Lago, Natalia
A1 Astudillo, Alma M
A1 Balsinde, Jesús
A1 Estivill-Torrús, Guillermo
A1 Rodríguez de Fonseca, Fernando
A1 Chun, Jerold
A1 López-Vales, Rubèn
K1 Demyelination
K1 Lysophosphatidic acid
K1 Microgria
K1 Neuroprotection
K1 Oligodendrocytes
K1 Spinal cord injury
K1 Potenciales evocados motores
K1 Lisofosfolípidos
K1 Ratas
K1 ratones consanguíneos C57BL
K1 Ratones transgénicos
K1 Microglía
K1 Actividad motora
K1 Oligodendroglía
K1 Receptores de ácidos lisofosfatídicos
K1 Médula espinal
K1 traumatismos de la médula espinal
K1 Factores de tiempo
K1 Animales recién nacidos
K1 Células cultivadas
K1 Muerte celular
K1 Corteza cerebral
K1 Enfermedades desmielinizantes
K1 Modelos de enfermedad en animales
AB UNLABELLEDLysophosphatidic 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.SIGNIFICANCE STATEMENTThis study reveals that LPA signaling via LPA receptor type 1 activation causes demyelination and functional deficits after spinal cord injury.
PB Society for Neuroscience
SN 0270-6474
YR 2015
FD 2015-07-15
LK http://hdl.handle.net/10668/2219
UL http://hdl.handle.net/10668/2219
LA en
NO Santos-Nogueira E, López-Serrano C, Hernández J, Lago N, Astudillo AM, Balsinde J, et al. Activation of Lysophosphatidic Acid Receptor Type 1 Contributes to Pathophysiology of Spinal Cord Injury. J. Neurosci.. 2015                         ; 35(28):10224-35
NO Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 5, 2025