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Journal of Molecular Neuroscience

, Volume 40, Issue 1–2, pp 185–195 | Cite as

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

  • Sharon Mexal
  • Ralph Berger
  • Judy Logel
  • Randal G. Ross
  • Robert Freedman
  • Sherry Leonard
Article
First Online:
Received:
Accepted:

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.

Keywords

Nicotinic receptor Schizophrenia Smoking Gene expression α7 CHRNA7 
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Notes

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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Copyright information

© Humana Press 2009

Authors and Affiliations

  • Sharon Mexal
    • 3
  • Ralph Berger
    • 1
  • Judy Logel
    • 1
  • Randal G. Ross
    • 1
  • Robert Freedman
    • 1
    • 2
  • Sherry Leonard
    • 1
    • 2
  1. 1.Department of PsychiatryUniversity of Colorado DenverAuroraUSA
  2. 2.The Veterans Affairs Medical Research ServiceDenverUSA
  3. 3.Cenomed BioSciencesIrvineUSA

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