Microglia play many beneficial roles in multiple sclerosis (MS) including the removal of neurotoxins and damaged myelin as well as by fostering repair. We previously found that the P2X4 positive allosteric modulator ivermectin increases myelin phagocytosis, promotes remyelination and improves symptoms recovery in experimental autoimmune encephalomyelitis (EAE). To define accurately the selectivity of the pharmacological treatment and the role of microglia in this protective effect, we used P2X4mCherryIN knock-in mice. In these mice P2X4 is substituted by a non-internalized P2X4mCherryIN (P2X4KI), leading to plasma membrane overexpression of P2X4 in all cells natively expressing P2X4 (CMV-P2X4KI) and in microglia/macrophages (CD11bCre-P2X4KI). Our data suggest that increased surface P2X4 expression effectively ameliorates EAE and that the therapeutic potential of targeting microglial P2X4 has a clear gender dimorphism.

More information:

• https://www.achucarro.org/laboratory/glia-matrix-biology/