Phosphodiesterase 10A (PDE10A) localization in the R6/2 mouse model of Huntington's disease

► PDE10A increases in the striatal projection neurons of R6/2 mice. Such accumulation occurs in the perikarya. ► PDE10 levels decrease in the whole striatum of R6/2 animals as observed in the densitometry studies. ► Accumulation of PDE10A might cause massive hydrolization of cyclic nucleotides damaging the cell. ► PDE10 decrease in the whole striatum is possibly due to its sequestration in the perikarya of projection neurons. ► PDE10A inhibitor TP10 lowers PDE10A levels efficiently in the medium spiny neurons perikarya. ► Cholinergic neurons, resistant to HD, contain moderate amounts of PDE10A, which do not change with TP10 treatment. ► PDE10A is present in the other subsets of striatal interneurons, where it is localized in the neuronal nuclei.