title: Involvement of P2X7 receptor in neuronal degeneration triggered by traumatic injury.
abstract: Axonal injury is a common feature of central nervous system insults that culminates with the death of the affected neurons, and an irreversible loss of function. Inflammation is an important component of the neurodegenerative process, where the microglia plays an important role by releasing proinflammatory factors as well as clearing the death neurons by phagocytosis. Here we have identified the purinergic signaling through the P2X7 receptor as an important component for the neuronal death in a model of optic nerve axotomy. We have found that in P2X7 receptor deficient mice there is a delayed loss of retinal ganglion cells and a decrease of phagocytic microglia at early times points after axotomy. In contralateral to the axotomy retinas, P2X7 receptor controlled the numbers of phagocytic microglia, suggesting that extracellular ATP could act as a danger signal activating the P2X7 receptor in mediating the loss of neurons in contralateral retinas. Finally, we show that intravitreal administration of the selective P2X7 receptor antagonist A438079 also delays axotomy-induced retinal ganglion cell death in retinas from wild type mice. Thus, our work demonstrates that P2X7 receptor signaling is involved in neuronal cell death after axonal injury, being P2X7 receptor antagonism a potential therapeutic strategy.
authors.affiliation: Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.|Departamento de Oftalmología, Facultad de Medicina. Universidad de Murcia, Murcia, Spain.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Nadal-Nicolás
authors.affiliation: Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.|Departamento de Oftalmología, Facultad de Medicina. Universidad de Murcia, Murcia, Spain.
authors.forename: Caridad
authors.initials: C
authors.lastname: Galindo-Romero
authors.affiliation: Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.|Departamento de Oftalmología, Facultad de Medicina. Universidad de Murcia, Murcia, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Valiente-Soriano
authors.affiliation: Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.|Unidad de Inflamación Molecular y Cirugía Experimental, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Barberà-Cremades
authors.affiliation: Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.|Unidad de Inflamación Molecular y Cirugía Experimental, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: deTorre-Minguela
authors.affiliation: Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.|Departamento de Oftalmología, Facultad de Medicina. Universidad de Murcia, Murcia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Salinas-Navarro
authors.affiliation: Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.|Unidad de Inflamación Molecular y Cirugía Experimental, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.|Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Pelegrín
authors.affiliation: Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.|Departamento de Oftalmología, Facultad de Medicina. Universidad de Murcia, Murcia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Agudo-Barriuso
mesh_terms: D000818:Animals; D019771:Axotomy; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020221:Optic Nerve Injuries / Q000378:metabolism* / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D058486:Receptors, Purinergic P2X7 / Q000172:deficiency / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors
chemical_list: C523668:3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methylpyridine; D058920:Purinergic P2X Receptor Antagonists; D011725:Pyridines; D058486:Receptors, Purinergic P2X7; D013777:Tetrazoles