Several studies revealed that both PDE10A, the cAMP/cGMP hydrolyzing enzyme highly enriched in mammalian striatum, and many proteins involved in synaptic transmission including cAMP/PKA transducing receptors, are post-translationally modified through S-palmitoylation. The altered expression of PDE10A and D2 receptor, previously demonstrated in dystonia animal models, could depend on a common modification of lipid post-translational modification that cause a dynamic relocation among different cellular compartments. Therefore, the aim of this project is to study the expression of PDE10A, adenosine (A2A) and dopaminergic (D1 and D2) receptors, that are involved in the synaptic transduction pathways mediated by cyclic nucleotides in the basal ganglia, in the dystonia Tor1a delta gag/+ mouse model. The experimental approach will include immunohistochemistry, confocal microscopy, biochemistry, physiology and the investigation of post-translational S-palmitoyl modification.
