Beta2* and beta4* nicotinic acetylcholine receptor expression changes with progressive parkinsonism in non-human primates.
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.
Kulak
Jennifer M
JM
Thomas Jefferson University, Department of Pathology, Anatomy and Cell Biology, 1020 Locust St., 521 JAH Philadelphia, PA 19107, USA. jenkulak@hotmail.com
Fan
Hong
H
Schneider
Jay S
JS
D000818:Animals; D001345:Autoradiography; D001384:Azetidines / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D007457:Iodine Radioisotopes / Q000494:pharmacology; D008251:Macaca; D018722:Nicotinic Agonists / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000096:biosynthesis*
C104288:A 85380; D001384:Azetidines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007457:Iodine Radioisotopes; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; C082748:epibatidine