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Related Experiment Videos

Smoking and schizophrenia: abnormal nicotinic receptor expression.

S Leonard1, C Breese, C Adams

  • 1Department of Psychiatry, University of Colorado Health Sciences Center, Denver, CO 80262, USA. sherry.leonard@uchsc.edu

European Journal of Pharmacology
|April 20, 2000
PubMed
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Schizophrenia neuropathophysiology involves neuronal nicotinic receptors. Abnormal gene expression and function of these receptors, particularly the alpha-7 nicotinic receptor, are implicated in the disease.

Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Neuronal nicotinic receptors play a role in schizophrenia neuropathophysiology.
  • Nicotine administration can normalize auditory evoked potential deficits in schizophrenia patients.
  • Reduced levels of high and low affinity nicotinic receptors are observed in postmortem brains of schizophrenic individuals.

Purpose of the Study:

  • To investigate the role of neuronal nicotinic receptors, specifically the alpha-7 gene, in the neuropathophysiology of schizophrenia.
  • To examine the expression and genetic structure of the human alpha-7 nicotinic receptor gene in schizophrenia.

Main Methods:

  • Analysis of auditory evoked potentials in response to nicotine.
  • Postmortem brain tissue analysis to quantify nicotinic receptor levels.

Related Experiment Videos

  • Genetic linkage studies to assess the chromosomal locus of the alpha-7 gene.
  • Gene cloning and expression analysis of the human alpha-7 gene, including investigation of duplications.
  • Administration of alpha-7 receptor antagonists to rodents to study gating deficits.

    • Main Results:

    • Nicotine normalized auditory evoked potential deficits in schizophrenia subjects.
    • Nicotinic receptors were decreased in the postmortem brains of schizophrenics.
    • The human alpha-7 nicotinic receptor gene locus (15q14) showed linkage to gating deficits.
    • Alpha-7 receptor antagonists induced gating deficits in rodents.
    • A partial duplication of the human alpha-7 gene was identified, expressed in normal subjects but absent in some schizophrenic patients.

    Conclusions:

    • Abnormal expression and function of the neuronal nicotinic receptor gene family are suggested in schizophrenia.
    • The alpha-7 nicotinic receptor and its gene appear to be critically involved in schizophrenia.
    • Genetic alterations, such as gene duplication, may contribute to schizophrenia pathogenesis.