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

There is growing evidence that alterations in calcium (Ca²⁺) homeostasis may play a role in processes of brain aging and neurodegeneration. There also is evidence that some of the altered Ca²⁺ homeostasis in hippocampal neurons may arise from an increased density of L-type voltage sensitive Ca²⁺ channels (L-VSCC). In the present studies, we tested the possibility that previously observed increases in functional L-VSCC with aging might be related to up-regulated gene/mRNA expression for Ca²⁺ channel subunits. A significant aging-related increase in mRNA content for the α(1D) subunit of the L-type VSCC was observed in hippocampus of aged F344 rats (25 months old) relative to young (4 months old) and middle-aged animals (13 months old), as assessed by both in situ hybridization analyses (densitometry and grain density) and ribonuclease protection assay (RPA). In RPA analyses, the α(1C) subunit mRNA also showed a significant increase in 25-month-old rats. No age changes were seen in mRNA for the β(1b) subunit of VSCC or for GAPDH, a standard control. The clearest increases in α(1D) mRNA expression were observed in subfield CA1, with little or no change seen in dentate gyrus. Although these results alone do not demonstrate that mRNA/gene expression changes contribute directly to changes in functional Ca²⁺ channels, they clearly fulfill an important prediction of that hypothesis. Therefore, these studies may have important implications for the role of gene expression in aging-dependent alterations in brain Ca²⁺ homeostasis. Copyright (C) 1998 Elsevier Science Inc.