In situ analysis of Na,K-ATPase alpha 1- and alpha 3-isoform mRNAs in aging rat hippocampus

Age-related changes in the expression of Na,K-ATPase alpha 1- and alpha 3-isoform mRNAs were analyzed by in situ hybridization in the Fischer-344 rat hippocampus. Quantification of signal density with cRNA probes in rat hippocampus at 3 months of age showed (a) alpha 1 content is 1.5 times higher in granule than in pyramidal cell layers, whereas alpha 3 content shows the opposite ratio and (b) alpha 3 label is found in large clusters related to messy cells and basket cells and in medium clusters corresponding to interneurons within the dendritic fields of CA1-3. In the 24-month-old rats as compared with the young animals, the alpha 1 signal is increased more than sevenfold in the dendritic fields and is not significantly changed in perikaryal layers, The alpha 3 signal is reduced about threefold (p < 0.0001, ANOVA, n = 6) in perikaryal layers, is almost completely absent over the interneurons, basket cells, and messy cells, and is not significantly changed in dendritic fields, These data indicate age-related, cell- and isoform-specific alterations in pretranslational regulation of Na,K-ATPase alpha isoforms, The striking changes in the dendritic fields, messy cells, and GABAergic basket cells and interneurons may constitute early and sensitive markers for age-related alterations in hippocampal function, before cell loss.