Pickering Chris, Ericson Mia, Söderpalm Bo
Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, P.O. Box 410, 405 30 Gothenburg, Sweden.
ISRN Psychiatry. 2013 Feb 19;2013:620361. doi: 10.1155/2013/620361. Print 2013.
Phencyclidine (PCP) mimics many aspects of schizophrenia, yet the underlying mechanism of neurochemical adaptation for PCP is unknown. We therefore used proteomics to study changes in the medial prefrontal cortex in animals with PCP-induced behavioural deficits. Male Wistar rats were injected with saline or 5 mg/kg phencyclidine for 5 days followed by two days of washout. Spontaneous alternation behaviour was tested in a Y-maze and then proteins were extracted from the medial prefrontal cortex. 2D-DIGE analysis followed by spot picking and protein identification with mass spectrometry then provided a list of differentially expressed proteins. Treatment with 5 mg/kg phencyclidine decreased the percentage of correct alternations in the Y-maze compared to saline-treated controls. Proteomics analysis of the medial prefrontal cortex found upregulation of 6 proteins (synapsin-1, Dpysl3, Aco2, Fscn1, Tuba1c, and Mapk1) and downregulation of 11 (Bin1, Dpysl2, Sugt1, ApoE, Psme1, ERp29, Pgam1, Uchl1, Ndufv2, Pcmt1, and Vdac1). A trend to upregulation was observed for Gnb4 and Capza2, while downregulation trends were noted for alpha-enolase and Fh. Many of the hits in this study concur with recent postmortem data from schizophrenic patients and this further validates the use of phencyclidine in preclinical translational research.
苯环利定（PCP）模拟精神分裂症的许多方面，然而PCP神经化学适应的潜在机制尚不清楚。因此，我们使用蛋白质组学来研究PCP诱导行为缺陷的动物内侧前额叶皮质的变化。雄性Wistar大鼠注射生理盐水或5mg/kg苯环利定，持续5天，随后停药2天。在Y迷宫中测试自发交替行为，然后从内侧前额叶皮质提取蛋白质。二维差异凝胶电泳（2D-DIGE）分析，随后进行斑点挑选和质谱蛋白质鉴定，从而提供差异表达蛋白质列表。与生理盐水处理的对照组相比，5mg/kg苯环利定处理降低了Y迷宫中正确交替的百分比。内侧前额叶皮质的蛋白质组学分析发现6种蛋白质（突触素-1、二氢嘧啶酶样蛋白3、乌头酸酶2、丝状肌动蛋白1、微管蛋白α1C和丝裂原活化蛋白激酶1）上调，11种蛋白质（衔接蛋白1、二氢嘧啶酶样蛋白2、Sugt1、载脂蛋白E、蛋白酶体激活因子1、内质网蛋白29、磷酸甘油酸变位酶1、泛素羧基末端水解酶L1、NADH脱氢酶（泛醌）Fe-S蛋白2、蛋白-L-异天冬氨酸甲基转移酶1和电压依赖性阴离子通道1）下调。观察到Gnb4和Capza2有上调趋势，而α-烯醇化酶和Fh有下调趋势。本研究中的许多发现与近期精神分裂症患者的尸检数据一致，这进一步验证了苯环利定在临床前转化研究中的应用。
