Anales RANF

S19-04 P2X4 RECEPTOR CONTROLS MICROGLIA ACTIVATION AND FAVOURS REMYELINATION IN AUTOIMMUNE ENCEPHALITIS Alazne Zabala 1 , Alejandro Montilla, Björn Rissiek 2 , Jon Gejo 1 , Alberto Perez- Samartín 1 , Abraham Martin 1 , Carlos Matute 1* and María Domercq 1* 1 Achucarro Basque Center for Neurosciences, CIBERNED and Departamento de Neurociencias, Universidad del País Vasco. E-48940 Leioa, Spain; 2 Department of Neurology, University Medical Center, Hamburg, Germany. Microglia survey the brain microenvironment for signals of injury or infection, and are essential for the initiation and resolution of pathogen- or tissue damage-induced inflammation. Understanding the mechanism of microglia responses during pathology is hence vital to promote regenerative responses. We observed that purinergic P2X4 receptor (P2X4R) was overexpressed in activated microglia in EAE and in human MS optic nerve samples . Here we analyzed the role of purinergic receptor P2X4 (P2X4R) in microglia/macrophages during autoimmune inflammation. Blockade of P2X4R signaling exacerbated clinical signs in the experimental autoimmune encephalomyelitis (EAE) model as well as favoured microglia activation to a pro-inflammatory phenotype and inhibited myelin phagocytosis. Moreover, P2X4R blockade in microglia halted oligodendrocyte differentiation in vitro and remyelination after lysolecithin-induced demyelination. Conversely, potentiation of P2X4R signaling by the allosteric modulator ivermectin (IVM) potentiated myelin phagocytosis, promoted the remyelination response and ameliorated clinical signs of EAE. We are currently studying the molecular mechanisms linking P2X4 activation to myelin phagocytosis. Our results provide evidence that P2X4Rs modulate microglia/macrophage inflammatory responses and identify IVM as a potential candidate among currently used drugs to promote the repair of myelin damage.