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 age. In situ hybridization for mGluR1 mRNA in the granule cell layer indicated significantly higher mRNA levels in the 24-month-old group as compared to the 5- and 15-month-old groups. However, mRNA levels of individual Purkinje neurons did not show age differences. Western blot analysis using antibody against the predominant isoform, mGluR1a, showed a decline in protein levels in the 24-month-old animals. In situ hybridization for IP3R type 1 mRNA in Purkinje neurons showed a slight but not significant decline in the 24-month-old group. Further assay of [3H]IP3 binding with cerebellar membranes showed significant reduction in Bmax values in the 15- and 24-month-old groups as compared to the 5-month-old group but Kd values were not changed. The decrease in mGluR1a receptor protein together with reduction in IP3R binding sites may play an important role in the decline in cerebellar functions with increasing age.