Differential expression of Na,K-ATPase alpha-isoform mRNAs in aging rat cerebellum

Age-dependent changes in the expression of Na,K-ATPase alpha 1- and alpha 3-mRNAs were analyzed in the rat cerebellum by in situ hybridization. In young rats, alpha 1-mRNA showed prominent labeling in the granular layer (GL) with moderate fine distribution in the molecular layer (ML), Purkinje cell layer (PCL), and white matter (WM) but no clusters over Purkinje cells (PCs). In old rats, alpha 1-mRNA remained unchanged in ML and PCL, but declined by 43% (P < 0.0001) in GL and increased by 624% (P < 0.0001) in WM. alpha 3-mRNA in young rats showed large clusters of label on stellate, basket, Golgi, and PCs and fine grains diffusely in ML, GL, and WM. In old rats, alpha 3-mRNA declined by 87% in ML, 83% in PCL, 84% per PC, and 89% in GL and increased by 111% in WM (all values P < 0.0001) relative to young rats. PC numbers were reduced by 30%, but the average area of PC profiles did not change significantly. In old rats, the specific cluster-like label related to alpha 3-mRNA on PCs, stellate, basket, and Golgi cells was lost. Immunocytochemistry of cerebellum and hippocampus showed no age-related change in the distribution and density of total catalytic polypeptide. Thus, the discordance between changes in the levels of mRNAs in neuronal layers and WM in the face of constant polypeptide levels indicates age-related changes in polypeptide turnover. Cell- and isoform-specificity of alpha-isoform mRNAs in aging rat cerebellum may reflect differential regulation underlying age-related impairments in signal transduction and motor learning.