Decreased GluR2(B) receptor subunit mRNA expression in cerebellar neurons at risk for degeneration.

Abstract

A decrease in levels of GluR2 (GluR-B) relative to other glutamate receptor subunits is correlated with increased Ca2+ permeability of non-NMDA glutamate receptor channels. Sustained Ca2+ influx mediated by GluR2 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 spastic Han-Wistar rat which is characterized by a progressive degeneration of cerebellar Purkinje cells and disarrangement of the granule cell layer. Combined Northern and slot blot studies detected decreased GluR2 subunit expression in mutant cerebellum relative to age-matched cerebellum. Quantitative in situ hybridization studies revealed decreased GluR2 mRNA expression in a population of Purkinje cells (78%) and in the granule cell layer (70%) in 30-day-old mutant cerebellum. Since there is little or no sign of cellular degeneration in mutant cerebellum at this age, we propose that decreased GluR2 mRNA expression in Han-Wistar cerebellar cells reflects an altered glutamate receptor that may aberrantly flux Ca2+ and thus contribute to progressive neuronal degeneration.