Up-regulation of alpha(1D) Ca2+ channel subunit mRNA expression in the hippocampus of aged F344 rats

There is growing evidence that alterations in calcium (Ca2+) homeostasis ma y play a role in processes of brain aging and neurodegeneration. There also is evidence that some of the altered Ca2+ homeostasis in hippocampal neuro ns may arise from an increased density of L-type voltage sensitive Ca2+ cha nnels (L-VSCC). In the present studies, we tested the possibility that prev iously observed increases in functional L-VSCC with aging might be related to up-regulated gene/mRNA expression for Ca2+ channel subunits. A significa nt aging-related increase in mRNA content for the alpha(1D) subunit of the L-type VSCC was observed in hippocampus of aged F344 rats (25 months old) r elative to young (4 months old) and middle-aged animals (13 months old), as assessed by both ill situ hybridization analyses (densitometry and grain d ensity) and ribonuclease protection assay (RPA). In RPA analyses, the alpha (1c) subunit mRNA also showed a significant increase in 25-month-old rats. No age changes were seen in mRNA for the beta(1b) subunit of VSCC or for GA PDH, a standard control. The dearest increases in cu,, mRNA expression were observed in subfield CA1 with little or no change seen in dentate gyrus. A lthough these results alone do not demonstrate that mRNA/gene expression ch anges contribute directly to changes in functional Ca2+ channels, they clea rly fulfill an important prediction of that hypothesis Therefore, these stu dies may have important implications for the role of gene expression in agi ng-dependent alterations in brain Ca2+ homeostasis. (C) 1999 Elsevier Scien ce Inc.