Anales RANF

S19-02 ADDRESSING THE ROLE OF P2X7 RECEPTORS IN PRIMARY DEMYELINATION AND REMYELINATION Susana Mato Achucarro Basque Center for Neuroscience and Department of Neuroscience, Leioa, Spain The contribution of P2x7 receptors to multiple sclerosis remains controversial as both detrimental and beneficial effects resulting from P2x7 receptor loss-of-function have been reported in autoimmune models of the disease. Here we investigated the relevance of P2x7 receptors to myelin damage and repair in the cuprizone model of T cell- independent demyelination. Toxic demyelination was associated to a robust upregulation of P2x7 receptors and NLPR3 inflammasome signaling molecules. Colocalization experiments indicated that upregulated P2x7 receptor expression in demyelinated white matter was mainly associated to microglial cells. Consistently, P2x7 knockout mice exhibited attenuated demyelination and reduced presence of microglia and reactive astrocytes and attenuated expression of inflammatory cytokines in response to cuprizone feeding. However, pharmacological blockade of P2x7 receptors during the remyelination phase did not improve the extent of myelin recovery nor attenuated glial reaction in damaged white matter in the time-window analyzed in this study. These results identify P2x7 receptors as mediators of primary demyelination and suggest potential applications, but also limitations, of the P2x7 receptor in supporting recovery from progressed pathological states.