DECREASED GLUR2(B) RECEPTOR SUBUNIT MESSENGER-RNA EXPRESSION IN CEREBELLAR NEURONS AT RISK FOR DEGENERATION

A decrease in levels of GluR2 (GluR-B) relative to other glutamate rec eptor subunits is correlated with increased Ca2+ permeability of non-N MDA glutamate receptor channels. Sustained Ca2+ influx mediated by Glu R2 through these channels may contribute partly to the pathogenesis of neurodegenerative disorders. We examined the expression of glutamate receptor subunit (GluR1-7) mRNAs in the cerebellum of the mutant spast ic Han-Wistar rat which is characterized by a progressive degeneration of cerebellar Purkinje cells and disarrangement of the granule cell l ayer. Combined Northern and slot blot studies detected decreased GluR2 subunit expression in mutant cerebellum relative to age-matched cereb ellum. Quantitative in situ hybridization studies revealed decreased G luR2 mRNA expression in a population of Purkinje cells (78%) and in th e granule cell layer (70%) in 30-day-old mutant cerebellum. Since ther e is little or no sign of cellular degeneration in mutant cerebellum a t this age, we propose that decreased GluR2 mRNA expression in Han-Wis tar cerebellar cells reflects an altered glutamate receptor that may a berrantly flux Ca2+ and thus contribute to progressive neuronal degene ration.