Nuclear localization of phosphodiesterase 10A (PDE10A) in the R6/2 mouse striatal interneurons

Introduction: Cyclic nucleotides play an important role as second messengers in the CNS. Intracellular concentrations of cAMP and cGMP are modulated by the rate of degradation by a variety of phosphodiesterases (PDEs). PDE10A is the single member of one of the newest PDE gene families. PDE10A has been observed in the brain mostly in the striatal projec- tion neurons [1]. However, we have previously observed [unpublished data], in the striatum, a number of PDE10 immunoreactive neurons that were not projection neurons. Methods: R6/2 mice and their wild type littermates were sacrificed at 5, 9, 13 weeks of age, and single and double label immunohistochemis- try were performed to identify the different neuronal subtypes of the striatum (medium spiny, choliner- gic, parvalbuminergic, somatos- tatinergic). Results: PDE10A was observed in all subtypes of striatal neurons. In the spiny projection neurons, PDE10A localized in the cytoplasm, whereas in the striatal interneurons, regardless of the sub- type, PDE10A displayed a clearly nuclear localization. This was true both for the wild type and for the R6/2 mice. Conclusions: Our study demonstrates that PDE10A is con- tained not only in the medium spiny neurons, but also in the striatal in- terneurons. Moreover, the different compartmentalization might be ex- plained by a different activity exert- ed by PDE10A between projection neurons and interneurons. Reference [1] Seeger TF, Bartlett B, Coskran TM, Culp JS, James LC, Krull DL, Lanfear J, Ryan AM, Schmidt CJ, Strick CA, Var- ghese AH, Williams RD, Wylie PG, Men- niti FS. Immunohistochemical localiza- tion of PDE10A in the rat brain. Brain Res. 2003; 985: 113-126.