AGE-DIFFERENCES IN THE EXPRESSION OF METABOTROPIC GLUTAMATE-RECEPTOR-1 AND INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR IN MOUSE CEREBELLUM

Age differences in the expression of cerebellar metabotropic glutamate receptor 1 (mGluR1) and inositol 1,4,5-trisphosphate receptor (IP3R) were investigated using male C57BL/6NNIA mice 5, 15 and 24 months of a ge. In situ hybridization for mGluR1 mRNA in the granule cell layer in dicated significantly higher mRNA levels in the 24-month-old group as compared to the 5- and 15-month-old groups. However, mRNA levels of in dividual Purkinje neurons did not show age differences. Western blot a nalysis using antibody against the predominant isoform, mGluR1a, showe d a decline in protein levels in the 24-month-old animals. In situ hyb ridization for IP3R type 1 mRNA in Purkinje neurons showed a slight bu t not significant decline in the 24-month-old group. Further assay of [H-3]IP3 binding with cerebellar membranes showed significant reductio n in B-max values in the 15- and 24-month-old groups as compared to th e 5-month-old group but K-d values were not changed. The decrease in m GluR1a receptor protein together with reduction in IP3R binding sites may play an important role in the decline in cerebellar functions with increasing age. (C) 1998 Elsevier Science Ireland Ltd.