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Involvement of alpha 6/alpha 3 neuronal nicotinic acetylcholine receptors in neuropsychiatric features of Dementia with Lewy bodies: [I-125]-alpha-conotoxin MII binding in the thalamus and striatum.

Lookup NU author(s): Dr Iwo Bohr, Dr Clive Ballard, Professor Ian McKeith, Emeritus Professor Robert Perry, Emeritus Professor Elaine Perry, Dr Jennifer Court, Dr Margaret Piggott

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Abstract

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 [I-125]-alpha-conotoxin MII ([I-125]-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 [I-125]-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). [I-125]-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 [I-125]-alpha-CtX MII binding and VH. Reductions in [I-125]-alpha-Ctx MII binding in caudate and putamen were paralleled by similar reductions in [I-125]PE21 binding. [I-125]PE21 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. (C) 2004 Elsevier Ireland Ltd. All rights reserved.


Publication metadata

Author(s): Ray M, Bohr I, McIntosh JM, Ballard C, McKeith I, Chalon S, Guilloteau D, Perry R, Perry E, Court JA, Piggott M

Publication type: Article

Publication status: Published

Journal: Neuroscience Letters

Year: 2004

Volume: 372

Issue: 3

Pages: 220-225

ISSN (print): 0304-3940

ISSN (electronic): 1872-7972

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.neulet.2004.09.042

DOI: 10.1016/j.neulet.2004.09.042


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