Effect of antipsychotic drugs on DISC1 and dysbindin expression in mouse frontal cortex and hippocampus
Effect of antipsychotic drugs on DISC1 and dysbindin expression in mouse frontal cortex and hippocampus
复制标题
DOI：
10.1007/s00702-005-0414-1
复制
发表时间：
2006-09-01
影响因子：
3.3
通讯作者：
Kunugi, H.
中科院分区：
文献类型：
--
作者：
Chiba, S.;Hashimoto, R.;Kunugi, H.
已报道精神分裂症易感基因DISC 1和DTNBP 1在精神分裂症患者脑中的表达改变;然而，抗精神病药物对这些基因表达水平的可能影响尚未研究。我们通过实时定量RT-PCR方法测定了这些基因在典型和非典型抗精神病药物慢性治疗的小鼠额叶皮层和海马中的mRNA表达水平。我们发现，非典型抗精神病药物奥氮平和利培酮，在临床相关剂量增加DISC 1在额叶皮层的表达水平，而一个典型的抗精神病药物，氟哌啶醇，没有。在任一脑区中均未观察到对dysbindin表达水平的显著影响。这些数据表明，先前的证据表明，精神分裂症患者死后大脑中dysbindin的表达减少，不太可能是一个简单的伪像的死前药物治疗。我们的研究结果还表明DISC 1在某些非典型抗精神病药物的治疗机制中的潜在作用。
Altered expression of Disrupted-In-Schizophrenia-1 (DISC1) and dysbindin (DTNBP1), susceptibility genes for schizophrenia, in schizophrenic brain has been reported; however, the possible effect of antipsychotics on the expression levels of these genes has not yet been studied. We measured the mRNA expression levels of these genes in frontal cortex and hippocampus of mice chronically treated with typical and atypical antipsychotics by a real-time quantitative RT-PCR method. We found that atypical antipsychotics, olanzapine and risperidone, in a clinically relevant dose increased DISC1 expression levels in frontal cortex, while a typical antipsychotic, haloperidol, did not. No significant effect on dysbindin expression levels was observed in either brain region. These data suggest that prior evidence of decreased expression of dysbindin in postmortem brain of schizophrenics is not likely to be a simple artifact of antemortem drug treatment. Our results also suggest a potential role of DISC1 in the therapeutic mechanisms of certain atypical antipsychotics.