The Role of ATP and P2X Purinoceptor 7 in the Development of Cerebral Tau

ATP release and signalling via the P2X7 receptor have been implicated in numerous pathological processes including neurodegeneration and may play a role in the development of tauopathies. We injected ATP analogue bzATP intraventricularly into C57BL/6 mice, pre-treated with either intraperitoneal P2X7R antagonist Brilliant Blue G (BBG) or vehicle. Behavioural outcomes, levels of phosphorylated tau, and immunohistochemical changes in astrocytes and microglia were assessed at 2 weeks and 3 months after treatment. We observed increased immobile time in the tail suspension test and poor performance on rotarod for bzATP-treated mice at 3 months post-treatment, which were diminished by BBG pre-treatment. Western blot revealed increased levels of phosphorylated tau in bzATP-treated mice compared to controls. Astrocytic marker GFAP showed increased periventricular staining at both 2 weeks and 3 months for bzATP-treated mice but microglial marker IBA1 showed no changes. In summary, ATP-P2X7R-mediated mechanisms lead to development of behavioural deficits and increased phosphorylated tau.M.Sc