P.1.002 Pharmacological characterisation of positive allosteric modulators acting on the metabotropic glutamate receptor 2

Abstract

3NP treated cells). After 12 h of 3NP addition, we observed Bax mitochondrial translocation, (26±5 Bax traslocation under control conditions vs 41±2 after 3NP treatment). Finally, scavengers of reactive oxygen species failed to prevent mitochondrial alterations, while cyclosporine A, but not Mdivi-1, prevented the generation of ROS. Data shown are mean±SEM, unless otherwise stated. Statistical significance of differences between groups was determined by ANOVA followed by a Newman–Keuls post hoc analysis. The level of statistical significance was set at P< 0.05. Conclusions: There was a direct correlation between formation of mitochondrial permeability transition pore and autophagy induced by 3NP treatment. Activation of autophagy preceded the apoptotic process and was mediated, at least partly, by formation of reactive oxygen species and mitochondrial permeability transition pore. 3NP induces mitochondrial swelling at short time, thus Drp1 is not able to migrate to the mitochondria. Moreover, cell apoptosis is activated through the intrinsic pathway.