Differential Regulation of α7 Nicotinic Receptor Gene (CHRNA7) Expression in Schizophrenic Smokers
- 13 August 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Molecular Neuroscience
- Vol. 40 (1-2), 185-195
- https://doi.org/10.1007/s12031-009-9233-4
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
This publication has 94 references indexed in Scilit:
- Regulation of a novel αN‐catenin splice variant in schizophrenic smokersNeuropsychiatric Genetics, Part B of the American Journal of Medical Genetics (AJMG), 2008
- Long-Term Upregulation of Protein Kinase A and Adenylate Cyclase Levels in Human SmokersJournal of Neuroscience, 2007
- Ubiquilin-1 Regulates Nicotine-induced Up-regulation of Neuronal Nicotinic Acetylcholine ReceptorsOnline Journal of Public Health Informatics, 2005
- Ric-3 Promotes Functional Expression of the Nicotinic Acetylcholine Receptor α7 Subunit in Mammalian CellsOnline Journal of Public Health Informatics, 2005
- The Role of Palmitoylation in Functional Expression of Nicotinic α7 ReceptorsJournal of Neuroscience, 2004
- Assembly of nicotinic α7 subunits inXenopusoocytes is partially blocked at the tetramer levelFEBS Letters, 2004
- Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergenceMolecular Psychiatry, 2004
- AR-R 17779, an α7 nicotinic agonist, improves learning and memory in ratsBehavioural Pharmacology, 1999
- NICOTINE EFFECTS ON WORKING MEMORYBehavioural Pharmacology, 1999
- Host Cell‐Specific Folding and Assembly of the Neuronal Nicotinic Acetylcholine Receptor α7 SubunitJournal of Neurochemistry, 1997