Cholinergic nicotinic receptor involvement in movement disorders associated with Lewy body diseases. An autoradiography study using [ 125 I]a-conotoxinMII in the striatum and thalamus I.J. Bohr a, * , M.A. Ray a , J.M. McIntosh b , S. Chalon c , D. Guilloteau c , I.G. McKeith d , R.H. Perry e , F. Clementi f , E.K. Perry a , J.A. Court a , M.A. Piggott a a Institute for Ageing and Health, Newcastle General Hospital, Centre Development in Clinical Brain Ageing, MRC Building, Westgate Road, Newcastle-upon-Tyne NE4 6BE, UK b Departments of Biology and Psychiatry, University of Utah, Salt Lake City, UT 84112, USA c INSERUM U316, Laboratory of Medical Biophysics and Pharmaceutics, University Francois Rabelais, Tours, France d Institute for Ageing and Health, Wolfson Research Centre, Newcastle General Hospital, Newcastle-upon-Tyne NE4 6BE, UK e Department of Neuropathology, Newcastle General Hospital, Newcastle-upon-Tyne NE4 6BE, UK f CNR Cellular and Molecular Pharmacology Centre, University of Milan, ViaVanVitelli 32, 20129 Milan, Italy Received 20 April 2004; revised 7 October 2004; accepted 13 October 2004 Available online 2 December 2004 Abstract The presence of a6 subunit containing nicotinic acetylcholine receptors on nigrostriatal dopaminergic neurons has been demonstrated in rodents and monkeys. [ 125 I]a-conotoxinMII is a radioligand that binds to a6, and also a3 subunits of nicotinic acetylcholine receptors (nAChRs). In the present study, we have compared the distribution of [ 125 I]a-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 À 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 À 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]a-conotoxinMII binding was significantly reduced in the centromedian nucleus in both DLB groups, and also in the parafascicular nucleus in the DLB À EPF group. In DLB + EPF and PD patients, there was decreased binding in the ventral lateral nucleus. This study demonstrates alterations of a6 and/or a3 nAChRs binding in DLB and PD, which are likely to relate to extra-pyramidal symptoms. D 2004 Elsevier Inc. All rights reserved. Keywords: Centromedial nucleus; Corpus striatum; Dopamine transporter; Lewy body disease; Neurodegenerative diseases; Nicotinic acetylcholine receptors; Parafascicular nucleus; Parkinson disease; Thalamus ventral lateral Introduction The neuropathological hallmark of dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) is the presence of Lewy bodies, which are a-synuclein-containing inclu- sions (Litvan et al., 1998). The clinical symptoms of DLB include dementia, recurrent visual hallucinations, and altered attention and fluctuating cognition, with many patients also developing a movement disorder resembling symptoms of PD such as limb rigidity, bradykinesia, and gait disorder (McKeith, 2002, 2004). The motor symptoms in both DLB and PD are associated with nigrostriatal pathology (Agid, 1991; Ince et al., 1995; Perry et al., 1990; Piggott and Marshall, 1996). In both these disorders, decreased levels of nicotinic acetylcholine receptors (nAChRs) with high affinity for ligands such as nicotine, epibatidine, and 5-IA-85380 have been reported in the striatum (Court et al., 2000; Guan et al., 2002; Martin-Ruiz et al., 2000; Perry et al., 1995; Pimlott et al., 2004). 0014-4886/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.expneurol.2004.10.004 * Corresponding author. Fax: +44 191444 44 02. E-mail address: iwo.bohr@ncl.ac.uk (I.J. Bohr). Experimental Neurology 191 (2005) 292 – 300 www.elsevier.com/locate/yexnr