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.