β2⁎ and β4⁎ nicotinic acetylcholine receptor expression changes with progressive parkinsonism in non-human primates

Abstract

Autoradiography was used to investigate nicotinic acetylcholine receptor (nAChR) binding in the brains of two groups of macaque monkeys with parkinsonism produced by different types of MPTP exposure: animals with cognitive deficits but no motor symptoms (motor-asymptomatic) and animals with typical motor symptoms of parkinsonism (motor-symptomatic). Motor-asymptomatic animals had no significant changes in [125I]epibatidine binding to β2⁎–β4⁎ nAChRs and [125I]A85380 binding to β2⁎ nAChRs in cognition-related cortical regions such as Broadman’s area 46, orbitofrontal cortex, the anterior cingulate sulcus and the hippocampus, but binding of both radioligands was decreased 70–80% in the caudate and putamen. Motor-symptomatic animals had decreases in β2⁎ and β4⁎ nAChR in the principal sulcus (40–60%), anterior cingulate sulcus (30–55%), and orbitofrontal cortex (30–41%), but not in the hippocampus, plus significant decreases in binding (70–80%) in the caudate and putamen. These results suggest that while nAChR expression is similarly decreased in the striatum of motor-asymptomatic and motor-symptomatic MPTP-treated monkeys, there are differences in β2⁎ and β4⁎ nAChR expression in cortical regions in these two conditions. Therefore, our data suggest that a therapeutic strategy based on nAChR agonist administration that might improve cognition in early PD patients may, due to a changing nAChR profile, have little or no effect on the same symptoms in more advanced patients.

Keywords

• Macaca fascicularis
• Macaca mulatta
• Macaca nemestrina
• Epibatidine
• A85380