Differential regulation of alpha7 nicotinic receptor gene (CHRNA7) expression in schizophrenic smokers.
Differential regulation of alpha7 nicotinic receptor gene (CHRNA7) expression in schizophrenic smokers.
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DOI：
10.1007/s12031-009-9233-4
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Leonard S
中科院分区：
文献类型：
--
作者：
Mexal S;Berger R;Logel J;Ross RG;Freedman R;Leonard S
α7神经元烟碱受体基因（CHRNA 7）通过遗传学和药理学研究被认为与精神分裂症的病理生理学有关。用[125 I]α-银环蛇毒素放射自显影法测定，精神分裂症受试者死后脑组织中α7* 受体的表达与非精神病对照组相比降低。大多数精神分裂症患者是重度吸烟者，血清可替宁水平高。吸烟改变精神分裂症海马多个基因表达及差异调节基因表达。我们研究了吸烟对同一组织中CHRNA 7表达的影响，发现吸烟对该基因的mRNA和蛋白质的表达有差异调节。CHRNA 7 mRNA和蛋白质水平在精神分裂症不吸烟者中显著低于对照不吸烟者，并在精神分裂症吸烟者中达到对照水平。在放射自显影研究中观察到α7* 受体的蛋白质充足但表面表达较低，提示受体的异常组装或运输。
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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