Age-related changes in parvalbumin-positive interneurons in the striatum, but not in the sensorimotor cortex in dystonic brains of the dt(sz) mutant hamster.

Abstract

In the dt(sz) hamster, a model of paroxysmal dystonia, an age-dependent increase in the activity of striatal projection neurons has been hypothesized to be based on a deficit of striatal parvalbumin-immunoreactive (PV(+)) interneurons at an age of most marked expression of dystonia (30-40 days of life). In the present study, the spontaneous age-dependent remission of paroxysmal dystonia in older dt(sz) hamsters (age>90 days) was found to coincide with a normalization of the density of striatal PV(+) interneurons. Furthermore, the arborization of these interneurons was lower in 31 day old dt(sz) hamsters, but was even higher in dt(sz) mutant at an age of >90 days than in control animals. Double-labeling with bromodeoxyuridine failed to show a retarded proliferation, while the number of interneurons with strong expression of PV mRNA was lower in young mutant hamsters. As shown by unaltered density of PV(+) interneurons in sensorimotor cortex of 31 day old dt(sz) hamsters, PV containing interneurons are not reduced throughout the whole brain at the sensitive age. The present data suggest that a retarded postnatal maturation of striatal PV(+) interneurons plays a critical role in paroxysmal dystonia.