Reduced expression of the molecular markers of dopaminergic neuronal atrophy in the aging rat brain.

Abstract

Expression of mRNAs encoding the dopamine transporter (DAT) and tyrosine hydroxylase (TH) in dopaminergic neurons of the substantia nigra (SN) was examined in young and aged Fischer 344 rats by in situ hybridization. Quantitative analysis revealed a statistically significant decline in both DAT and TH mRNA expression in 24-month-old rats in comparison to 6-month-old rats. In addition, it was noted that DAT mRNA expression tended to decrease by 18 months, while TH mRNA reduction did not occur until 24 months. The age-related loss of DAT and TH mRNA expressions was accompanied by diminished expression of mRNA for a neuronal growth-associated protein GAP-43, but not for SCG10 or alpha 1-tubulin. The loss of GAP-43 mRNA became evident when both DAT and TH gene expression declined with advanced age. Our findings indicate that DAT may be a marker of atrophy in dopamine neurons during normal aging.