Abstract
Heavy smoking and schizophrenia are diversely associated with nicotinic acetylcholine receptor expression, as was shown for brain and lymphocytes. Most studies so far have not systematically differentiated between schizophrenia smokers and non-smokers and were confined either to in vivo or post-mortem study approaches. In order to avoid variable in vivo influences or post-mortem bias, we used stably transformed B-lymphoblast cultures derived from healthy and schizophrenia subjects stratified for smoking versus non-smoking in order to differentiate these clinical conditions with regard to nicotinic acetylcholine receptor expression and regulation. Receptor quantities were measured using [3H]-nicotine and [3H]-epibatidine binding. At baseline, [3H]-nicotine binding was not statistically different between healthy smokers and never-smokers (1.59 ± 0.73 vs. 1.26 ± 0.91 fmol/106 cells), while it was reduced in schizophrenia smokers compared to healthy smokers (1.05 ± 0.69 fmol vs. 1.44 ± 0.84/106 cells, P = 0.01). In schizophrenia, baseline [3H]-nicotine correlated inversely with higher PANSS negative subscale scores. After long-term nicotine incubation (1 μM), [3H]-nicotine binding increased in the group of schizophrenia smokers only (from 1.05 ± 0.69 to 1.54 ± 0.77 fmol/106 cells, P = 0.013), while [3H]-epibatidine binding decreased in this group (4.52 ± 1.52 to 3.82 ± 1.38 fmol/106 cells, P = 0.038). Our data are in further support of a decrease of nicotinic acetylcholine receptor expression in schizophrenia linked to negative psychotic symptoms, which may be counter-regulated by nicotine exposure.
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Acknowledgments
The study was supported by an in-house grant of the Research Commission (Forschungskommission) of the Medical Faculty of the Heinrich-Heine-University Düsseldorf (S. F., U. H., C. L.) and by the Deutsche Forschungsgemeinschaft (DFG) as part of the study: “Attentional Network, Nicotine-Dependence and Alpha4Beta2 nAch Receptor Genotype in Healthy Subjects and Schizophrenic Patients” (G.W.:Wi1316/7-1) which was conducted within the framework of the National Priority Program “Nicotine: Molecular and physiological effects in CNS” supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)
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C. Luckhaus and U. Henning contributed equally to this work.
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Luckhaus, C., Henning, U., Ferrea, S. et al. Nicotinic acetylcholine receptor expression on B-lymphoblasts of healthy versus schizophrenic subjects stratified for smoking: [3H]-nicotine binding is decreased in schizophrenia and correlates with negative symptoms. J Neural Transm 119, 587–595 (2012). https://doi.org/10.1007/s00702-011-0743-1
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DOI: https://doi.org/10.1007/s00702-011-0743-1