Alteration of the PAC1 Receptor Expression in the Basal Ganglia of MPTP-Induced Parkinsonian Macaque Monkeys.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a well-known neuropeptide with strong neurotrophic and neuroprotective effects. PACAP exerts its protective actions via three G protein-coupled receptors: the specific Pac1 receptor (Pac1R) and the Vpac1/Vpac2 receptors, the neuroprotective effects being mainly mediated by the Pac1R. The protective role of PACAP in models of Parkinson's disease and other neurodegenerative diseases is now well-established in both in vitro and in vivo studies. PACAP and its receptors occur in the mammalian brain, including regions associated with Parkinson's disease. PACAP receptor upregulation or downregulation has been reported in several injury models or human diseases, but no data are available on alterations of receptor expression in Parkinson's disease. The model closest to the human disease is the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced macaque model. Therefore, our present aim was to evaluate changes in Pac1R expression in basal ganglia related to Parkinson's disease in a macaque model. Monkeys were rendered parkinsonian with MPTP, and striatum, pallidum, and cortex were evaluated for Pac1R immunostaining. We found that Pac1R immunosignal was markedly reduced in the caudate nucleus, putamen, and internal and external parts of the globus pallidus, while the immunoreactivity remained unchanged in the cortex of MPTP-treated parkinsonian monkey brains. This decrease was attenuated in some brain areas in monkeys treated with L-DOPA. The strong, specific decrease of the PACAP receptor immunosignal in the basal ganglia of parkinsonian macaque monkey brains suggests that the PACAP/Pac1R system may play an important role in the development/progression of the disease.