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The underlying mechanisms of various types of hereditary paroxysmal dyskinesias are still unknown but basal ganglia dysfunctions seem to play a critical role. In fact, recent immunohistochemical studies in the dtsz hamster, a genetic animal model of paroxysmal nonkinesiogenic choreoathetosis, have demonstrated a deficit of striatal parvalbumin-immunreactive (PV+) GABAergic interneurons.
These results prompted us to investigate if the deficit of striatal interneurons is restricted to those which express PV. Therefore, in the present study we investigated the density of striatal calretinin-immunreactive (CR+) interneurons, also positive for GABA, GAD67 and in part for choline acetyltransferase, and nitric oxide synthase-immunreactive (NOS+) interneurons, which co-express somatostatin and neuropeptid Y. The cells were counted by using a stereological counting method in a blinded fashion. A significant reduction in the density of striatal CR+ (-20%) and NOS+ (-21%) interneurons was found in dtsz hamsters in comparison to age- and gender-matched non-dystonic control animals.
The present results demonstrate that the deficit of striatal interneurons is not restricted to PV+ ones. Thus, decreased densities of CR+ and NOS+ interneurons probably contribute to abnormal striatal connections, leading to a decreased activity of basal ganglia output structures as demonstrated by previous electrophysiological studies in mutant hamsters. Further studies have to clarify if spontaneous remission of dystonia in dtsz hamsters coincides with a normalization of CR+ and NOS+ interneuron density and whether the ratio between striatal projection and interneurons is altered.
Supported by the Deutsche Forschungsgemeinschaft (Ri 845-1/2).