Antipsychotics alter the protein expression levels of β-catenin and GSK-3 in the rat medial prefrontal cortex and striatum
Antipsychotics alter the protein expression levels of β-catenin and GSK-3 in the rat medial prefrontal cortex and striatum
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DOI：
10.1016/j.biopsych.2004.11.036
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发表时间：
2005-03-01
影响因子：
10.6
通讯作者：
Rushlow, W
中科院分区：
文献类型：
--
作者：
Alimohamad, H;Rajakumar, N;Rushlow, W
背景资料：已经证明精神分裂症患者改变了脑中几种Wnt相关蛋白的水平和/或磷酸化状态，包括β-连环蛋白和GSK-3，并且可能代表精神分裂症的易感基因座。本研究旨在探讨抗精神病药物对β-catenin和糖原合成酶激酶-3的影响。方法：采用免疫印迹法和免疫细胞化学方法，观察急性、亚慢性和慢性给药后抗精神病药物对β-catenin和糖原合成酶激酶-3的影响。特异性的反应进行了测试，使用额外的药物，如氟西汀，安非他明和丙戊酸。氯氮平、氟哌啶醇或利培酮给药后，β-连环蛋白和糖原合成酶激酶-3总蛋白水平显著升高。GSK-3的磷酸化状态也增加，但磷酸化β-连环蛋白水平不受影响。其他药物化合物，与雷氯必利，坏没有影响GSK-3或β-连环蛋白的蛋白水平或distribution.Conclusions：靶向β-连环蛋白和GSK-3是一个共同的特点，无论类抗精神病药物，似乎是由D-2多巴胺受体介导的。因此，β-连环蛋白和GSK-3的变化可能是抗精神病药物能够产生行为改变的机制之一。
Background: It has been demonstrated that schizophrenics have altered levels and/or phosphorylation states of several Wnt related proteins in the brain, including beta-catenin and GSK-3, and may represent susceptibility loci for schizophrenia. The current study was conducted to assess the effects of antipsychotics on beta-catenin and glycogen synthase kinase-3.Methods: Western blotting and immunocytochemistry were employed to investigate the effects of antipsychotics on beta-catenin and glycogen synthase kinase-3 following acute, subchronic and chronic drug administration. Specificity of the response was tested using additional drugs such as fluoxetine, amphetamine and valproic acid.Results. Significant increases in the levels of beta-catenin and glycogen synthase kinase-3 total protein were identified following administration of clozapine, haloperidol or risperidone. The phosphorylation state of GSK-3 was also increased but phosphorylated beta-catenin levels were unaffected. Other drug compounds, with the exception of raclopride, bad no effect on either GSK-3 or beta-catenin protein levels or distribution.Conclusions: Targeting of beta-catenin and GSK-3 is a common feature of antipsychotics regardless of class and appears to be mediated by D-2 dopamine receptors. Therefore changes in beta-catenin and GSK-3 may represent one of the mechanisms through which antipsychotics are able to exert behavioral changes.