Beta2* and beta4* nicotinic acetylcholine receptor expression changes with progressive parkinsonism in non-human...

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 beta2*-beta4* nAChRs and [125I]A85380 binding to beta2* 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 beta2* and beta4* 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 beta2* and beta4* 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.