Ricerc@Sapienza

Clinical and experimental data point to the basal ganglia network dysfunction as the main culprit in DYT1 dystonia pathophysiology. Our recent work showed, in the basal ganglia circuit of a transgenic DYT1 mouse model, an altered expression of the enzyme phosphodiesterase 10A (PDE10A). PDE10A is highly enriched in the GABAergic medium spiny projection neurons of the mammalian striatum, and reaches the basal ganglia output structures through the transport along the striatal projections. Here we want to study the expression of PDE10A and A2A receptor proteins, that are both involved in basal ganglia cyclic nucleotide pathway, in a Tor1a¿gag/+ mice dystonia model. Our approach will include immunohistochemistry, confocal microscopy, biochemistry, and physiology. We therefore propose to investigate the striatal output pathways in Tor1a¿gag/+ mice in order to characterize the alterations of the basal ganglia network in DYT1 dystonia. More importantly, we will test the effects of in vivo mouse pharmacological treatment in rescuing the alterations of basal ganglia activity.