Age-related changes in striatal nitric oxide synthase-immunoreactive interneurones in the dystonic dtsz mutant hamster.

Abstract

The dt(sz) mutant hamster represents a model of paroxysmal dyskinesia in which dystonic episodes can be age-dependently induced by stress. GABAergic interneurones which co-express calcium binding proteins were found to be reduced in the striatum of the dt(sz) mutant. Other types of striatal interneurones have so far not been examined. In the present study, we therefore determined the density of nitric oxide synthase (NOS)-immunoreactive interneurones in the striatum of the dt(sz) mutant in comparison with nondystonic control hamsters. At the age of most marked expression of dystonia (30-40 days of life), the density of NOS-positive interneurones was decreased in the striatum of dt(sz) hamsters (-21%) in comparison with age-matched nondystonic control hamsters. Spontaneous remission of dystonia (age >90 days) coincided with a normalization of the density of NOS-reactive interneurones within the whole striatum of dt(sz) hamsters, but there remained a reduced density in distinct subregions. Together with previous findings the present data indicate that the development of striatal interneurones is retarded in mutant hamsters. The age-related deficit of NOS-reactive interneurones may at least in part contribute to an abnormal activity of striatal GABAergic projection neurones and thereby to the age-dependent dystonic syndrome in the dt(sz) mutant.