Cholinergic nicotinic receptor involvement in movement disorders associated with Lewy body diseases. An autoradiography study using [(125)I]alpha-conotoxinMII in the striatum and thalamus.
The presence of alpha6 subunit containing nicotinic acetylcholine receptors on nigrostriatal dopaminergic neurons has been demonstrated in rodents and monkeys. [(125)I]alpha-conotoxinMII is a radioligand that binds to alpha6, and also alpha3 subunits of nicotinic acetylcholine receptors (nAChRs). In the present study, we have compared the distribution of [(125)I]alpha-conotoxinMII binding in post mortem human tissue from four groups of patients: individuals with dementia with Lewy bodies displaying extra-pyramidal features (DLB + EPF), DLB without extra-pyramidal features (DLB - EPF) Parkinson's disease without dementia (PD) and age-matched controls. Reduced binding was observed in the putamen and caudate in PD and both DLB groups. In DLB patients, the decline was greater in DLB + EPF compared to DLB - EPF group. The declines in nicotinic receptor binding in the striatum were in part paralleled by reductions in the striatal dopamine transporter. In the thalamus, [(125)I]alpha-conotoxinMII binding was significantly reduced in the centromedian nucleus in both DLB groups, and also in the parafascicular nucleus in the DLB - EPF group. In DLB + EPF and PD patients, there was decreased binding in the ventral lateral nucleus. This study demonstrates alterations of alpha6 and/or alpha3 nAChRs binding in DLB and PD, which are likely to relate to extra-pyramidal symptoms.
Bohr
I J
IJ
Institute for Ageing and Health, Newcastle General Hospital, Centre Development in Clinical Brain Ageing, MRC Building, Westgate Road, Newcastle-upon-Tyne NE4 6BE, UK. iwo.bohr@ncl.ac.uk
Ray
M A
MA
McIntosh
J M
JM
Chalon
S
S
Guilloteau
D
D
McKeith
I G
IG
Perry
R H
RH
Clementi
F
F
Perry
E K
EK
Court
J A
JA
Piggott
M A
MA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D001345:Autoradiography; D001667:Binding, Competitive; D020916:Conotoxins / Q000378:metabolism* / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D017072:Neostriatum / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D011978:Receptors, Nicotinic / Q000032:analysis / Q000378:metabolism*; D013788:Thalamus / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology
D020916:Conotoxins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C098872:alpha-conotoxin MII; C104518:nicotinic receptor alpha6