Original ArticlesUp-regulation of α1D Ca2+ channel subunit mRNA expression in the hippocampus of aged F344 rats
Section snippets
Subjects
Subjects were male Fischer-344 (F344) rats acquired from the National Institute on Aging-sponsored colony at Harlan Sprague–Dawley (Indianapolis, IN). Upon arrival, rats were housed in individual cages in an isolated colony reserved for specific-pathogen-free animals. All rats had ad libitum access to food and water, and were maintained on a 12:12 h light:dark cycle. Rats were either 4 (young, n = 12), 13 (middle-aged, n = 12) or 25 (aged, n = 12) months old when euthanized by rapid
Results
A number of individuals in the aged group showed gross pathologies that are commonly associated with the aging process in the F344 rat strain. Included were splenomegaly (8 out of 12 animals), testicular hypertrophy (6 out of 12 animals), and pituitary tumors (2 out of 12 animals). There was no correlation between pathology and age-related changes in mRNA expression in individual animals. Animals with pituitary tumors were not included in the data analysis.
Discussion
The results of this study provide direct evidence that mRNAs encoding Ca2+ channel-related subunits are increased with brain aging, apparently in a subunit and region-specific manner. Significant increases in α1D mRNA were preferentially observed in subfield CA1 (Fig. 2), using both densitometric and grain density analysis. However, grain density analysis revealed an increase in CA3 as well, primarily reflecting differences between the middle-aged and aged groups. Significant aging effects were
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