Low dopamine transporter mRNA levels in midbrain regions containing calbindin

The dopamine transporter (DAT) is the site at which the neurotoxic metabolite of MPTP gains access to midbrain dopaminergic (DA) neurons. However, not all midbrain DA neurons degenerate following MPTP treatment. The midbrain DA neurons that contain the calcium-binding protein, calbindin-D28k (CALB), are relatively invulnerable to MPTP toxicity, compared with DA neurons that lack CALB. Using in situ hybridization and immunocytochemical staining techniques in the rat and mouse, we now report that there is as much as 10 fold less DAT mRNA in regions where DA neurons contain CALB compared with regions where DA neurons lack CALB. These data suggest that specific midbrain DA neurons are invulnerable to MPTP toxicity not only because they contain CALB, but also because they have relatively low DAT activity.