Decreased GluR2(B) receptor subunit mRNA expression in cerebellar neurons at risk for degeneration.
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.
Margulies
J E
JE
Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine 90024.
Cohen
R W
RW
Levine
M S
MS
Watson
J B
JB
D000818:Animals; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D006651:Histocytochemistry; D017403:In Situ Hybridization; D009410:Nerve Degeneration / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000096:biosynthesis*
D018076:DNA, Complementary; D015347:RNA Probes; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D002118:Calcium