Decrease of nicotinic receptors in the nigrostriatal system in Parkinson's disease.
Smoking is associated with a lower incidence of Parkinson's disease (PD), which might be related to a neuroprotective action of nicotine. Postmortem studies have shown a decrease of cerebral nicotinic acetylcholine receptors (nAChRs) in PD. In this study, we evaluated the decrease of nAChRs in PD in vivo using positron emission tomography (PET), and we explored the relationship between nAChRs density and PD severity using both clinical scores and the measurement of striatal dopaminergic function. Thirteen nondemented patients with PD underwent two PET scans, one with 6-[(18)F]fluoro-3,4-dihydroxy-L-phenylalanine (6-[(18)F]fluoro-L-DOPA) to measure the dopaminergic function and another with 2-[(18)F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine (2-[(18)F]fluoro-A-85380), a radiotracer with high affinity for the nAChRs. Distribution volumes (DVs) of 2-[(18)F]fluoro-A-85380 measured in the PD group were compared with those obtained from six nonsmoking healthy controls, with regions-of-interest and voxel-based approaches. Both analyses showed a significant (P <0.05) decrease of 2-[(18)F]fluoro-A-85380 DV in the striatum (-10%) and substantia nigra (-14.9%) in PD patients. Despite the wide range of PD stages, no correlation was found between DV and the clinical and PET markers of PD severity.
Kas
Aurélie
A
URA CNRS-CEA 2210, MIRCen, I2BM/DSV, Orsay, France. aurelie.kas@cea.fr
Bottlaender
Michel
M
Gallezot
Jean Dominique
JD
Vidailhet
Marie
M
Villafane
Gabriel
G
Grégoire
Marie Claude
MC
Coulon
Christine
C
Valette
Héric
H
Dollé
Frédéric
F
Ribeiro
Maria-Joao
MJ
Hantraye
Philippe
P
Remy
Philippe
P
D000328:Adult; D000368:Aged; D001384:Azetidines / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology; D049268:Positron-Emission Tomography; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012907:Smoking; D013378:Substantia Nigra / Q000378:metabolism*
C104288:A 85380; D001384:Azetidines; D005462:Fluorine Radioisotopes; D011978:Receptors, Nicotinic; D004298:Dopamine