Involvement of alpha6/alpha3 neuronal nicotinic acetylcholine receptors in neuropsychiatric features of Dementia with Lewy bodies: [(125)I]-alpha-conotoxin MII binding in the thalamus and striatum.
Dementia with Lewy bodies (DLB) is a neurodegenerative disease associated with a range of neuropsychiatric symptoms and reduced expression of neuronal nicotinic acetylcholine receptors (nAChRs) in neocortex, hippocampus, thalamus and basal ganglia. To determine whether there are selective associations between alterations in alpha6/alpha3 neuronal nicotinic acetylcholine receptors (nAChRs) and the two key neuropsychiatric features of DLB, impaired consciousness (IC) and visual hallucinations (VH), quantitative [(125)I]-alpha-conotoxin MII ([(125)I]-alpha-Ctx MII) autoradiography was undertaken on 28 people with DLB and 15 control cases from the Newcastle Brain Bank. There was a highly significant overall trend for reduced thalamic [(125)I]-alpha-Ctx MII binding in DLB (p < 0.001), with significant deficits in the centromedian, ventral lateral and ventroposterior medial thalamic nuclei (p < 0.05), together with caudate and putamen (p < 0.001). [(125)I]-alpha-Ctx MII binding was significantly lower in DLB cases with IC than without IC in the putamen (p < 0.05), however there was no significant association between [(125)I]-alpha-Ctx MII binding and VH. Reductions in [(125)I]-alpha-Ctx MII binding in caudate and putamen were paralleled by similar reductions in [(125)I]PE2I binding. [(125)I]PE2I binding was also significantly lower in DLB cases with IC than without IC in the caudate (p < 0.05) and putamen (p < 0.001). These results demonstrate that deficits in alpha6/alpha3 nAChRs occur in specific brain regions in DLB, may in part be related to the loss of dopaminergic neurons and may contribute to the development of impaired consciousness in the disorder.
Ray
Melissa
M
Institute for Ageing and Health, University of Newcastle upon Tyne, MRC Building, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK.
Bohr
Iwo
I
McIntosh
J Michael
JM
Ballard
Clive
C
McKeith
Ian
I
Chalon
Sylvie
S
Guilloteau
Denis
D
Perry
Robert
R
Perry
Elaine
E
Court
J A
JA
Piggott
Margaret
M
D000368:Aged; D000369:Aged, 80 and over; D001345:Autoradiography; D001921:Brain / Q000473:pathology; D020916:Conotoxins / Q000378:metabolism*; D003243:Consciousness / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006212:Hallucinations / Q000378:metabolism / Q000523:psychology; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology* / Q000523:psychology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism / Q000502:physiology*; D012727:Sex Characteristics; D013788:Thalamus / Q000378:metabolism*
D020916:Conotoxins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C098872:alpha-conotoxin MII; C104518:nicotinic receptor alpha6; D004298:Dopamine