title: Involvement of P2X4 receptors in hippocampal microglial activation after status epilepticus.
abstract: Within the central nervous system, functions of the ATP-gated receptor-channel P2X4 (P2X4R) are still poorly understood, yet P2X4R activation in neurons and microglia coincides with high or pathological neuronal activities. In this study, we investigated the potential involvement of P2X4R in microglial functions in a model of kainate (KA)-induced status epilepticus (SE). We found that SE was associated with an induction of P2X4R expression in the hippocampus, mostly localized in activated microglial cells. In P2X4R-deficient mice, behavioral responses during KA-induced SE were unaltered. However, 48h post SE specific features of microglial activation, such as cell recruitment and upregulation of voltage-dependent potassium channels were impaired in P2X4R-deficient mice, whereas the expression and function of other microglial purinergic receptors remained unaffected. Consistent with the role of P2X4R in activity-dependent degenerative processes, the CA1 area was partially protected from SE-induced neuronal death in P2X4R-deficient mice compared with wild-type animals. Our findings demonstrate that P2X4Rs are brought into play during neuronal hyperexcitability and that they control specific aspects of microglial activation. Our results also suggest that P2X4Rs contribute to excitotoxic damages by regulating microglial activation.
authors.affiliation: Institut de Génomique Fonctionnelle, Labex ICST, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Université Montpellier, Montpellier, France. lauriane.ulmann@igf.cnrs.fr
authors.forename: Lauriane
authors.initials: L
authors.lastname: Ulmann
authors.forename: Françoise
authors.initials: F
authors.lastname: Levavasseur
authors.forename: Elena
authors.initials: E
authors.lastname: Avignone
authors.forename: Ronan
authors.initials: R
authors.lastname: Peyroutou
authors.forename: Hélène
authors.initials: H
authors.lastname: Hirbec
authors.forename: Etienne
authors.initials: E
authors.lastname: Audinat
authors.forename: François
authors.initials: F
authors.lastname: Rassendren
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009924:Organ Culture Techniques; D058848:Receptors, Purinergic P2X4 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D013226:Status Epilepticus / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D058848:Receptors, Purinergic P2X4
keywords: ATP; P2X receptors; epilepsy; hippocampus; inflammation; microglial cells