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Differential Regulation of α7 Nicotinic Receptor Gene (CHRNA7) Expression in Schizophrenic Smokers

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An Erratum to this article was published on 10 November 2009

Abstract

The α7 neuronal nicotinic receptor gene (CHRNA7) has been implicated in the pathophysiology of schizophrenia by genetic and pharmacological studies. Expression of the α7* receptor, as measured by [125I]α-bungarotoxin autoradiography, is decreased in postmortem brain of schizophrenic subjects compared to non-mentally ill controls. Most schizophrenic patients are heavy smokers, with high levels of serum cotinine. Smoking changes the expression of multiple genes and differentially regulates gene expression in schizophrenic hippocampus. We examined the effects of smoking on CHRNA7 expression in the same tissue and find that smoking differentially regulates expression of both mRNA and protein for this gene. CHRNA7 mRNA and protein levels are significantly lower in schizophrenic nonsmokers compared to control nonsmokers and are brought to control levels in schizophrenic smokers. Sufficient protein but low surface expression of the α7* receptor, seen in the autoradiographic studies, suggests aberrant assembly or trafficking of the receptor.

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References

  • Abecasis, G. R., & Cookson, W. O. C. (2000). GOLD—Graphical Overview of Linkage Disequilibrium. Bioinformatics, 16, 182–183.

    Article  CAS  PubMed  Google Scholar 

  • Adler, L. E., Waldo, M. C., Nagamoto, H. T., Baker, N., Franks, R., Bickford-Wimer, P. C., et al. (1991). 10 Years of studies on P50 sensory gating - A review and considerations for future studies. Schizophrenia Research, 4, 329.

    Article  Google Scholar 

  • Adler, L. E., Hoffer, L. D., Wiser, A., & Freedman, R. (1993). Normalization of auditory physiology by cigarette smoking in schizophrenic patients. American Journal of Psychiatry, 150, 1856–1861.

    CAS  PubMed  Google Scholar 

  • Adler, L. E., Olincy, A., Waldo, M. C., Harris, J. G., Griffith, J., Stevens, K., et al. (1998). Schizophrenia, sensory gating, and nicotinic receptors. Schizophrenia Bulletin, 24, 189–202.

    CAS  PubMed  Google Scholar 

  • Albuquerque, E. X., Pereira, E. F., Braga, M. F., Matsubayashi, H., & Alkondon, M. (1998). Neuronal nicotinic receptors modulate synaptic function in the hippocampus and are sensitive to blockade by the convulsant strychnine and by the anti-Parkinson drug amantadine. Toxicology Letters, 102–103, 211–218.

    Article  PubMed  Google Scholar 

  • American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Arlington: American Psychiatric Association.

    Google Scholar 

  • Blount, P., & Merlie, J. P. (1991). BIP associates with newly synthesized subunits of the mouse muscle nicotinic receptor. Journal of Cell Biology, 113, 1125–1132.

    Article  CAS  PubMed  Google Scholar 

  • Breese, C. R., Lee, M. J., Adams, C. E., Sullivan, B., Logel, J., Gillen, K. M., et al. (2000). Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia. Neuropsychopharmacology, 23, 351–364.

    Article  CAS  PubMed  Google Scholar 

  • Chang, W., Gelman, M. S., & Prives, J. M. (1997). Calnexin-dependent enhancement of nicotinic acetylcholine receptor assembly and surface expression. Journal of Biological Chemistry, 272, 28925–28932.

    Article  CAS  PubMed  Google Scholar 

  • Christianson, J. C., & Green, W. N. (2004). Regulation of nicotinic receptor expression by the ubiquitin-proteasome system. EMBO Journal, 23, 4156–4165.

    Article  CAS  PubMed  Google Scholar 

  • Cooper, S. T., & Millar, N. S. (1997). Host cell-specific folding and assembly of the neuronal nicotinic acetylcholine receptor a7. Journal of Neurochemistry, 68, 2140–2151.

    Article  CAS  PubMed  Google Scholar 

  • Cooper, E., Couturier, S., & Ballivet, M. (1991). Pentameric structure and subunit stoichiometry of a neuronal nicotinic acetylcholine receptor. Nature, 350, 235–238.

    Article  CAS  PubMed  Google Scholar 

  • Court, J., Spurden, D., Lloyd, S., McKeith, I., Ballard, C., Cairns, N., et al. (1999). Neuronal nicotinic receptors in dementia with Lewy bodies and schizophrenia: Alpha-bungarotoxin and nicotine binding in the thalamus. Journal of Neurochemistry, 73, 1590–1597.

    Article  CAS  PubMed  Google Scholar 

  • Dalack, G. W., Healy, D. J., & Meador-Woodruff, J. H. (1998). Nicotine dependence in schizophrenia: Clinical phenomena and laboratory findings. American Journal of Psychiatry, 155, 1490–1501.

    CAS  PubMed  Google Scholar 

  • de Leon, J., & Diaz, F. J. (2005). A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophrenia Research, 76, 135–157.

    Article  PubMed  Google Scholar 

  • De Luca, V., Wong, A. H. C., Muller, D. J., Wong, G. W. H., Tyndale, R. F., & Kennedy, J. L. (2004). Evidence of association between smoking and alpha 7 nicotinic receptor subunit gene in schizophrenia patients. Neuropsychopharmacology, 29, 1522–1526.

    Article  PubMed  CAS  Google Scholar 

  • Drisdel, R. C., Manzana, E., & Green, W. N. (2004). The role of palmitoylation in functional expression of nicotinic alpha7 receptors. Journal of Neuroscience, 24, 10502–10510.

    Article  CAS  PubMed  Google Scholar 

  • Endicott, J., Andreasen, N. C., & Spitzer, R. L. (1978). Family History-Research Diagnostic Criteria, Research Assessment and Training Unit, New York State Psychiatric Institute, NY.

  • Ficklin, M. B., Zhao, S., & Feng, G. (2005). Ubiquilin-1 regulates nicotine-induced up-regulation of neuronal nicotinic acetylcholine receptors. Journal of Biological Chemistry, 280, 34088–34095.

    Article  CAS  PubMed  Google Scholar 

  • First, M. B., Gibbon, M., Spitzer, R. L., & Williams, J. B. W. (1996). Structured clinical interview for axis I DSM-IV disorders-non-patient edition (SCID-I/NP, Version 2.0). New York: Biometrics Research.

    Google Scholar 

  • Freedman, R., Hall, M., Adler, L. E., & Leonard, S. (1995). Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia. Biological Psychiatry, 38, 22–33.

    Article  CAS  PubMed  Google Scholar 

  • Freedman, R., Coon, H., MylesWorsley, M., OrrUrtreger, A., Olincy, A., Davis, A., et al. (1997). Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proceedings of the National Academy of Sciences of the United States of America, 94, 587–592.

    Article  CAS  PubMed  Google Scholar 

  • Freedman, R., Adler, L. E., & Leonard, S. (1999). Alternative phenotypes for the complex genetics of schizophrenia. Biological Psychiatry, 45, 551–558.

    Article  CAS  PubMed  Google Scholar 

  • Freedman, R., Leonard, S., Olincy, A., Kaufmann, C. A., Malaspina, D., Cloninger, C. R., et al. (2001). Evidence for the multigenic inheritance of schizophrenia. American Journal of Medical Genetics, 105, 794–800.

    Article  CAS  PubMed  Google Scholar 

  • Freedman, R., Olincy, A., Buchanan, R. W., Harris, J. G., Gold, J. M., Johnson, L., et al. (2008). Initial phase 2 trial of a nicotinic agonist in schizophrenia. American Journal of Psychiatry, 165(8), 1040–1047.

    Article  PubMed  Google Scholar 

  • Gault, J., Robinson, M., Berger, R., Drebing, C., Logel, J., Hopkins, J., et al. (1998). Genomic organization and partial duplication of the human a7 neuronal nicotinic acetylcholine receptor gene. Genomics, 52, 173–185.

    Article  CAS  PubMed  Google Scholar 

  • Gault, J., Hopkins, J., Berger, R., Drebing, C., Logel, J., Walton, K., et al. (2003). Comparison of polymorphisms in the a7 nicotinic receptor gene and its partial duplication in schizophrenic and control subjects. American Journal of Medical Genetics, 123B, 39–49.

    Article  PubMed  Google Scholar 

  • George, T. P., & Krystal, J. H. (2000). Comorbidity of psychiatric and substance abuse disorders. Current Opinion in Psychiatry, 13, 327–331.

    Article  Google Scholar 

  • George, T. P., Vessicchio, J. C., Termine, A., Sahady, D. M., Head, C. A., Pepper, W. T., et al. (2002). Effects of smoking abstinence on visuospatial working memory function in schizophrenia. Neuropsychopharmacology, 26, 75–85.

    Article  PubMed  Google Scholar 

  • Grady, S., Marks, M. J., Wonnacott, S., & Collins, A. C. (1992). Characterization of nicotinic receptor-mediated [3H]dopamine release from synaptosomes prepared from mouse striatum. Journal of Neurochemistry, 59, 848–856.

    Article  CAS  PubMed  Google Scholar 

  • Green, W. N., & Millar, N. S. (1995). Ion-channel assembly. Trends in Neurosciences, 18, 280–287.

    Article  CAS  PubMed  Google Scholar 

  • Guan, Z. Z., Zhang, X., Blennow, K., & Nordberg, A. (1999). Decreased protein level of nicotinic receptor alpha7 subunit in the frontal cortex from schizophrenic brain. NeuroReport, 10, 1779–1782.

    Article  CAS  PubMed  Google Scholar 

  • Guo, J. Z., Tredway, T. L., & Chiappinelli, V. A. (1998). Glutamate and GABA release are enhanced by different subtypes of presynaptic nicotinic receptors in the lateral geniculate nucleus. Journal of Neuroscience, 18, 1963–1969.

    CAS  PubMed  Google Scholar 

  • Harrison, P. J., & Weinberger, D. R. (2005). Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Molecular Psychiatry, 10, 40–68.

    Article  CAS  PubMed  Google Scholar 

  • Holzman, P. S., Proctor, L. R., & Hughes, D. W. (1973). Eye-tracking patterns in schizophrenia. Science, 181, 179–181.

    Article  CAS  PubMed  Google Scholar 

  • Hope, B. T., Nagarkar, D., Leonard, S., & Wise, R. A. (2007). Long-term upregulation of protein kinase a and adenylate cyclase levels in human smokers. Journal of Neuroscience, 27, 1964–1972.

    Article  CAS  PubMed  Google Scholar 

  • Jeanclos, E. M., Lin, L., Treuil, M. W., Rao, J., DeCoster, M. A., & Anand, R. (2001). The chaperone protein 14–3-3 eta interacts with the nicotinic acetylcholine receptor alpha 4 subunit - Evidence for a dynamic role in subunit stabilization. Journal of Biological Chemistry, 276, 28281–28290.

    Article  CAS  PubMed  Google Scholar 

  • Jones, I. W., & Wonnacott, S. (2004). Precise localization of alpha 7 nicotinic acetylcholine receptors on glutamatergic axon terminals in the rat ventral tegmental area. Journal of Neuroscience, 24, 11244–11252.

    Article  CAS  PubMed  Google Scholar 

  • Kaiser, S., & Wonnacott, S. (2000). alpha-Bungarotoxin-sensitive nicotinic receptors indirectly modulate [H-3]dopamine release in rat striatal slices via glutamate release. Molecular Pharmacology, 58, 312–318.

    CAS  PubMed  Google Scholar 

  • Kaufmann, C. A., Suarez, B., Malaspina, D., Pepple, J., Svrakic, D., Markel, P. D., et al. (1998). NIMH genetics initiative millenium schizophrenia consortium: linkage analysis of African-American pedigrees. American Journal of Medical Genetics, 81, 282–289.

    Article  CAS  PubMed  Google Scholar 

  • Keller, S. H., & Taylor, P. (1999). Determinants responsible for assembly of the nicotinic acetylcholine receptor. Journal of General Physiology, 113, 171–176.

    Article  CAS  PubMed  Google Scholar 

  • Kristiansen, L. V., & Meador-Woodruff, J. H. (2005). Abnormal striatal expression of transcripts encoding NMDA interacting PSD proteins in schizophrenia, bipolar disorder and major depression. Schizophrenia Research, 78, 87–93.

    PubMed  Google Scholar 

  • Kuehn, B. M. (2006). Link between smoking and mental illness may lead to treatments. Jama-Journal of the American Medical Association, 295, 483–484.

    Article  CAS  Google Scholar 

  • Kumari, V., & Postma, P. (2005). Nicotine use in schizophrenia: The self medication hypotheses. Neuroscience and Biobehavioral Reviews, 29, 1021.

    Article  CAS  PubMed  Google Scholar 

  • Leonard, S. (2003). Consequences of low levels of nicotinic acetylcholine receptors in schizophrenia for drug development. Drug Development Research, 60, 127–136.

    Article  CAS  Google Scholar 

  • Leonard, S., & Bertrand, D. (2001). Neuronal nicotinic receptors: From structure to function. Nicotine & Tobacco Research, 3, 203–223.

    Article  CAS  Google Scholar 

  • Leonard, S., Logel, J., Luthman, D., Casanova, M., Kirch, D., & Freedman, R. (1993). Biological stability of mRNA isolated from human postmortem brain collections. Biological Psychiatry, 33, 456–466.

    Article  CAS  PubMed  Google Scholar 

  • Leonard, S., Gault, J., Moore, T., Hopkins, J., Robinson, M., Olincy, A., et al. (1998). Further investigation of a chromosome 15 locus in schizophrenia: Analysis of affected sibpairs from the NIMH genetics initiative. American Journal of Medical Genetics, 81, 308–312.

    Article  CAS  PubMed  Google Scholar 

  • Leonard, S., Adler, L. E., Benhammou, K., Berger, R., Breese, C. R., Drebing, C., et al. (2001). Smoking and mental illness. Pharmacology, Biochemistry and Behavior, 70, 561–570.

    Article  CAS  Google Scholar 

  • Leonard, S., Gault, J., Hopkins, J., Logel, J., Vianzon, R., Short, M., et al. (2002). Association of promoter variants in the alpha 7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia. Archives of General Psychiatry, 59, 1085–1096.

    Article  CAS  PubMed  Google Scholar 

  • Leonard, S., Berger, R., Mexal, S., Walton, K., & Freedman, R. (2005). Comparison of gene expression in human cultured skin fibroblasts and postmortem brain: Neuregulin-1 expression is decreased in primary skin fibroblasts of schizophrenic subjects. Online, Program No. 815.7 Abstract Viewer/Itinerary Planner Society for Neuroscience.

  • Leonard, S., Mexal, S., Berger, R., Olincy, A., & Freedman, R. (2007). Smoking and schizophrenia: Evidence for self medication. Schizophrenia Bulletin, 33, 262–263.

    Google Scholar 

  • Levin, E. D., Bettegowda, C., Blosser, J., & Gordon, J. (1999). AR-R17779, an alpha 7 nicotinic agonist, improves learning and memory in rats. Behavioural Pharmacology, 10, 675–680.

    Article  CAS  PubMed  Google Scholar 

  • Levin, E. D., McClernon, F. J., & Rezvani, A. H. (2006). Nicotinic effects on cognitive function: Behavioral characterization, pharmacological specification, and anatomic localization. Psychopharmacology, 184, 523–539.

    Article  CAS  PubMed  Google Scholar 

  • Levy, R. B., & Aoki, C. (2002). alpha 7 nicotinic acetylcholine receptors occur at postsynaptic densities of AMPA receptor-positive and -negative excitatory synapses in rat sensory cortex. Journal of Neuroscience, 22, 5001–5015.

    CAS  PubMed  Google Scholar 

  • Levy, D. L., Holzman, P. S., Matthysse, S., & Mendell, N. R. (1993). Eye tracking dysfunction and schizophrenia - a critical perspective. Schizophrenia Bulletin, 19, 461–536.

    CAS  PubMed  Google Scholar 

  • Li, J. Z., Vawter, M. P., Walsh, D. M., Tomita, H., Evans, S. J., Choudary, P. V., et al. (2004). Systematic changes in gene expression in postmortem human brains associated with tissue pH and terminal medical conditions. Human Molecular Genetics, 13, 609–616.

    Article  CAS  PubMed  Google Scholar 

  • Lindstrom, J. (1997). Nicotinic acetylcholine receptors in health and disease. [Review] [135 refs]. Molecular Neurobiology, 15, 193–222.

    Article  CAS  PubMed  Google Scholar 

  • Liu, C. M., Hwu, H. G., Lin, M. W., Ou-Yang, W. C., Lee, S. F. C., Fann, C. S. J., et al. (2001). Suggestive evidence for linkage of schizophrenia to markers at chromosome 15q13–14 in Taiwanese families. American Journal of Medical Genetics, 105, 658–661.

    Article  CAS  PubMed  Google Scholar 

  • MacDermott, A. B., Role, L. W., & Siegelbaum, S. A. (1999). Presynaptic ionotropic receptors and the control of transmitter release [Review]. Annual Review of Neuroscience, 22, 443–485.

    Article  CAS  PubMed  Google Scholar 

  • Maggi, L., Le Magueresse, C., Changeux, J. P., & Cherubini, E. (2003). Nicotine activates immature "silent" connections in the developing hippocampus. Proceedings of the National Academy of Sciences of the United States of America, 100, 2059–2064.

    Article  CAS  PubMed  Google Scholar 

  • Marks, M. J., Stitzel, J. A., & Collins, A. C. (1986). A dose-response analysis of nicotine tolerance and receptor changes in two inbred mouse strains. Journal of Pharmacology and Experimental Therapeutics, 239, 358–364.

    CAS  PubMed  Google Scholar 

  • Marutle, A., Zhang, X., Court, J., Piggott, M., Johnson, M., Perry, R., et al. (2001). Laminar distribution of nicotinic receptor subtypes in cortical regions in schizophrenia. Journal of Chemical Neuroanatomy, 22, 115–126.

    Article  CAS  PubMed  Google Scholar 

  • Mexal, S., Frank, M., Berger, R., Adams, C. E., Ross, R. G., Freedman, R., et al. (2005). Differential modulation of gene expression in the NMDA postsynaptic density of schizophrenic and control smokers. Molecular Brain Research, 139, 317–332.

    Article  CAS  PubMed  Google Scholar 

  • Mexal, S., Berger, R., Adams, C. E., Ross, R. G., Freedman, R., & Leonard, S. (2006). Brain pH has a significant impact on human postmortem hippocampal gene expression profiles. Brain Research, 1106, 1–11.

    Article  CAS  PubMed  Google Scholar 

  • Mexal, S., Berger, R., Pearce, L., Barton, A., Logel, J., Adams, C. E., et al. (2007). Regulation of a novel aN-catenin splice variant in schizophrenic smokers. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 147B(6), 759–768.

    Article  CAS  Google Scholar 

  • Nicke, A., Thurau, H., Sadtler, S., Rettinger, J., & Schmalzing, G. (2004). Assembly of nicotinic alpha7 subunits in Xenopus oocytes is partially blocked at the tetramer level. FEBS Letters, 575, 52–58.

    Article  CAS  PubMed  Google Scholar 

  • Olincy, A., Young, D. A., & Freedman, R. (1997). Increased levels of the nicotine metabolite cotinine in schizophrenic smokers compared to other smokers. Biological Psychiatry, 42, 1–5.

    Article  CAS  PubMed  Google Scholar 

  • Olincy, A., Ross, R. G., Young, D. A., Roath, M., & Freedman, R. (1998). Improvement in smooth pursuit eye movements after cigarette smoking in schizophrenic patients. Neuropsychopharmacology, 18, 175–185.

    Article  CAS  PubMed  Google Scholar 

  • Olincy, A., Johnson, L. L., & Ross, R. G. (2003). Differential effects of cigarette smoking on performance of a smooth pursuit and a saccadic eye movement task in schizophrenia. Psychiatry Research, 117, 223–236.

    Article  PubMed  Google Scholar 

  • Olincy, A., Harris, J. G., Johnson, L. L., Pender, V., Kongs, S., Allensworth, D., et al. (2006). Proof-of-concept trial of an alpha 7 nicotinic agonist in schizophrenia. Archives of General Psychiatry, 63, 630–638.

    Article  CAS  PubMed  Google Scholar 

  • Ren, X. Q., Cheng, S. B., Treuil, M. W., Mukherjee, J., Rao, J., Braunewell, K. H., et al. (2005). Structural determinants of alpha4beta2 nicotinic acetylcholine receptor trafficking. Journal of Neuroscience, 25, 6676–6686.

    Article  CAS  PubMed  Google Scholar 

  • Riley, B. P., Makoff, A. M., Magudi-Carter, M., Jenkins, T. J., Williamson, R., Collier, D. A., et al. (2000). Haplotype transmission disequilibrium and evidence for linkage of the CHRNA7 gene region to schizophrenia in Southern African Bantu families. American Journal of Medical Genetics, 96, 196–201.

    Article  CAS  PubMed  Google Scholar 

  • Riley, B., Williamson, M., Collier, D., Wilkie, H., & Makoff, A. (2002). A 3-Mb map of a large segmental duplication overlapping the alpha 7-nicotinic acetylcholine receptor gene (CHRNA7) at human 15q13–q14. Genomics, 79, 197–209.

    Article  CAS  PubMed  Google Scholar 

  • Ross, R. G., Olincy, A., Harris, J. G., Radant, A., Adler, L. E., & Freedman, R. (1998). Anticipatory saccades during smooth pursuit eye movements and familial transmission of schizophrenia. Biological Psychiatry, 44, 690–697.

    Article  CAS  PubMed  Google Scholar 

  • Rousseau, S. J., Jones, I. W., Pullar, I. A., & Wonnacott, S. (2005). Presynaptic alpha 7 and non-alpha 7 nicotinic acetylcholine receptors modulate [H-3]D-aspartate release from rat frontal cortex in vitro. Neuropharmacology, 49, 59–72.

    Article  CAS  PubMed  Google Scholar 

  • Sallette, J., Bohler, S., Benoit, P., Soudant, M., Pons, S., Le Novere, N., et al. (2004). An extracellular protein microdomain controls up-regulation of neuronal nicotinic acetylcholine receptors by nicotine. Journal of Biological Chemistry, 279, 18767–18775.

    Article  CAS  PubMed  Google Scholar 

  • Sallette, J., Pons, S., Devillers-Thiery, A., Soudant, M., Prado de Carvalho, L., Changeux, J. P., et al. (2005). Nicotine upregulates its own receptors through enhanced intracellular maturation. Neuron, 46, 595–607.

    Article  CAS  PubMed  Google Scholar 

  • Sambrook, J., & Russell, D. W. (2001). Molecular cloning: A laboratory manual (3rd ed.). Cold Spring Harbor: Cold Spring Harbor Laboratory Press.

    Google Scholar 

  • Shoop, R. D., Martone, M. E., Yamada, N., Ellisman, M. H., & Berg, D. K. (1999). Neuronal acetylcholine receptors with alpha7 subunits are concentrated on somatic spines for synaptic signaling in embryonic chick ciliary ganglia. Journal of Neuroscience, 19, 692–704.

    CAS  PubMed  Google Scholar 

  • Simosky, J. K., Stevens, K. E., Kern, W. R., & Freedman, R. (2001). Intragastric DMXB-A, an alpha 7 nicotinic agonist, improves deficient sensory inhibition in DBA/2 mice. Biological Psychiatry, 50, 493–500.

    Article  CAS  PubMed  Google Scholar 

  • Stevens, K. E., Kem, W. R., Mahnir, V. M., & Freedman, R. (1998). Selective alpha7-nicotinic agonists normalize inhibition of auditory response in DBA mice. Psychopharmacology, 136, 320–327.

    Article  CAS  PubMed  Google Scholar 

  • Stöber, G., Saar, K., Rüschendorf, F., Meyer, J., Nürnberg, G., Jatzke, S., et al. (2000). Splitting schizophrenia: Periodic catatonia-susceptibility locus on chromosome 15q15. American Journal of Human Genetics, 67, 1201–1207.

    PubMed  Google Scholar 

  • Tsuang, D. W., Skol, A. D., Faraone, S. V., Bingham, S., Young, K. A., Prabhudesai, S., et al. (2001). Examination of genetic linkage of chromosome 15 to schizophrenia in a large veterans affairs cooperative study sample. American Journal of Medical Genetics, 105, 662–668.

    Article  CAS  PubMed  Google Scholar 

  • Vijayaraghavan, S., Pugh, P. C., Zhang, Z.-W., Rathouz, M. M., & Berg, D. K. (1992). Nicotinic receptors that bind a-bungarotoxin on neurons raise intracellular free Ca++. Neuron, 8, 353–362.

    Article  CAS  PubMed  Google Scholar 

  • Wanamaker, C. P., Christianson, J. C., & Green, W. N. (2003). Regulation of nicotinic acetylcholine receptor assembly. Annals of the New York Academy of Sciences, 998, 66–80.

    Article  CAS  PubMed  Google Scholar 

  • Weiser, M., Levin, E. D., George, T. P., Newhouse, P. A., & Leonard, S. (2004). Nicotinic receptor modulation of attention: An endophenotype for therapeutic drug development. Biological Psychiatry, 55, 152S–152S.

    Google Scholar 

  • Williams, M. E., Burton, B., Urrutia, A., Shcherbatko, A., Chavez-Noriega, L. E., Cohen, C. J., et al. (2005). Ric-3 promotes functional expression of the nicotinic acetylcholine receptor alpha7 subunit in mammalian cells. Journal of Biological Chemistry, 280, 1257–1263.

    Article  CAS  PubMed  Google Scholar 

  • Wonnacott, S. (1986). a-Bungarotoxin binds to low-affinity nicotine binding sites in rat brain. Journal of Neurochemistry, 47, 1706–1712.

    Article  CAS  PubMed  Google Scholar 

  • Wonnacott, S. (1997). Presynaptic nicotinic ACh receptors. [Review] [76 refs]. Trends in Neurosciences, 20, 92–98.

    Article  CAS  PubMed  Google Scholar 

  • Wonnacott, S., Sidhpura, N., & Balfour, D. J. K. (2005). Nicotine: from molecular mechanisms to behaviour. Current Opinion in Pharmacology, 5, 53–59.

    Article  CAS  PubMed  Google Scholar 

  • Xu, J. Z., Pato, M. T., Dalla Torre, C., Medeiros, H., Carvalho, C., Basile, V. S., et al. (2001). Evidence for linkage disequilibrium between the alpha 7- nicotinic receptor gene (CHRNA7) locus and schizophrenia in Azorean families. American Journal of Medical Genetics, 105, 669–674.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the National Institute on Drug Abuse (NIDA) DA09457, the National Institute on Mental Health (NIMH) MH081177 and MH068582, and the Veterans Affairs Medical Research Service. We are grateful to Bernadette Sullivan and Katy Walton for technical assistance.

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Authors and Affiliations

  1. Department of Psychiatry, University of Colorado Denver, Mail Stop 8344, P.O. Box 6511, Aurora, CO, 80045, USA

    Ralph Berger, Judy Logel, Randal G. Ross, Robert Freedman & Sherry Leonard

  2. The Veterans Affairs Medical Research Service, Denver, CO, USA

    Robert Freedman & Sherry Leonard

  3. Cenomed BioSciences, Irvine, CA, USA

    Sharon Mexal

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  1. Sharon Mexal
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  2. Ralph Berger
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  3. Judy Logel
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  6. Sherry Leonard
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Correspondence to Sherry Leonard.

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Proceedings of the XIII International Symposium on Cholinergic Mechanisms

An erratum to this article can be found at http://dx.doi.org/10.1007/s12031-009-9303-7

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Mexal, S., Berger, R., Logel, J. et al. Differential Regulation of α7 Nicotinic Receptor Gene (CHRNA7) Expression in Schizophrenic Smokers. J Mol Neurosci 40, 185–195 (2010). https://doi.org/10.1007/s12031-009-9233-4

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