Cenomed BioSciences, Irvine, CA, USA.
J Mol Neurosci. 2010 Jan;40(1-2):185-95. doi: 10.1007/s12031-009-9233-4. Epub 2009 Aug 13.
The alpha7 neuronal nicotinic receptor gene (CHRNA7) has been implicated in the pathophysiology of schizophrenia by genetic and pharmacological studies. Expression of the alpha7* receptor, as measured by [(125)I]alpha-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 alpha7* receptor, seen in the autoradiographic studies, suggests aberrant assembly or trafficking of the receptor.
α7 型神经元烟碱型乙酰胆碱受体基因 (CHRNA7) 通过遗传和药理学研究被认为与精神分裂症的病理生理学有关。与非精神疾病对照者相比，精神分裂症患者死后大脑中 [(125)I]α-银环蛇毒素放射自显影测量的 α7*受体表达减少。大多数精神分裂症患者是重度吸烟者，血清可铁宁水平较高。吸烟会改变多个基因的表达，并在精神分裂症海马体中差异调节基因表达。我们研究了吸烟对同一组织中 CHRNA7 表达的影响，发现吸烟对该基因的 mRNA 和蛋白表达都有差异调节作用。与对照组非吸烟者相比，精神分裂症非吸烟者的 CHRNA7 mRNA 和蛋白水平明显降低，而精神分裂症吸烟者的水平则与对照组相当。在 autoradiographic 研究中观察到的受体的表面表达虽然充足，但数量较少，这表明受体的组装或运输异常。
