Brain α7 nicotinic acetylcholine receptors in MPTP-lesioned monkeys and parkinsonian patients

L-DOPA-induced dyskinesias (LID) appear in the majority of Parkinson's disease (PD) patients. Nicotinic acetylcholine (nACh) receptor-mediated signaling has been implicated in PD and LID and modulation of brain alpha 7 nACh receptors might be a potential therapeutic target for PD. This study used [I-125]alpha-Bungarotoxin autoradiography to investigate alpha 7 nACh receptors in LID in post-mortem brains from PD patients (n = 14) and control subjects (n =11), and from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys treated with saline (n = 5), L-DOPA (n = 4) or L-DOPA + 2-methy1-6-(phenyle thynyl)pyridine (MPEP) (n = 5), and control monkeys (n = 4). MPEP is the prototypal metabotropic glutamate 5 (mGlu5) receptor antagonist; it reduced the development of LID in these monkeys. [I-125]alpha-Bungarotoxin specific binding to striatal and pallidal alpha 7 nACh receptors were only increased in L-DOPA-treated dyskinetic MPTP monkeys as compared to controls, saline and L-DOPA + MPEP MPTP monkeys; dyskinesia scores correlated positively with this binding. The total group of Parkinsonian patients had higher [I-125]alpha-Bungarotoxin specific binding compared to controls in the caudate nucleus but not in the putamen. PD patients without motor complications had higher [I-125]alpha-Bungarotoxin specific binding compared to controls only in the caudate nucleus. PD patients with LID only had higher [I-125]alpha-Bungarotoxin specific binding compared to controls in the caudate nucleus and compared to those without motor complications and controls in the putamen. PD patients with wearing-off only, had [I-125]alpha-Bungarotoxin specific binding at control values in the caudate nucleus and lower in the putamen. Reduced motor complications were associated with normal striatal alpha 7 nACh receptors, suggesting the potential of this receptor to manage motor complications in PD. (C) 2016 Elsevier Inc. All rights reserved.