Dyck Bailee A, Skoblenick Kevin J, Castellano Jessica M, Ki Kitty, Thomas Nancy, Mishra Ram K
Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Synapse. 2009 Aug;63(8):662-72. doi: 10.1002/syn.20643.
Recent studies on the phosphoprotein synapsin II have revealed reduced expression in postmortem medial prefrontal cortex tissues from subjects with schizophrenia, and chronic antipsychotic drug treatment has resulted in concurrent increases in synapsin II mRNA and protein levels. Collectively, this research suggests a role of synapsin II in the pathophysiology of schizophrenia; however, whether synapsin II plays a causal role in this disease process still remains unclear. Therefore, the goal of this investigation was to examine whether synapsin II knockout mice display behavioral abnormalities commonly expressed in preclinical animal models of schizophrenia, namely deficits in prepulse inhibition (PPI), decreased social behavior, and locomotor hyperactivity. Results indicate that mice with knockout of the synapsin II gene demonstrate deficits in PPI at three prepulse intensities (67, 70, and 73 dB), along with deficits in habituation to startle to a 110 dB acoustic pulse. Knockout animals also expressed decreased social behavior and increased locomotor activity when compared to wildtype and heterozygous populations. Complete knockout of the synapsin II gene was confirmed in postmortem brain tissues via immunoblotting. In conclusion, these results confirm that synapsin II knockout mice display behavioral endophenotypes similar to established preclinical animal models of schizophrenia, and lend support to the notion that abnormalities in synapsin II expression may play a causal role in the underlying pathophysiological mechanisms of schizophrenia.
近期关于磷蛋白突触素II的研究表明，精神分裂症患者死后内侧前额叶皮质组织中该蛋白表达降低，而长期使用抗精神病药物治疗会使突触素II的mRNA和蛋白水平同时升高。总体而言，这项研究表明突触素II在精神分裂症的病理生理学中发挥作用；然而，突触素II是否在该疾病过程中起因果作用仍不清楚。因此，本研究的目的是检验突触素II基因敲除小鼠是否表现出精神分裂症临床前动物模型中常见的行为异常，即前脉冲抑制（PPI）缺陷、社交行为减少和运动活动亢进。结果表明，突触素II基因敲除的小鼠在三种前脉冲前脉冲前强度（67、70和73分贝）下表现出PPI缺陷，同时对110分贝声脉冲的惊吓习惯化也存在缺陷。与野生型和杂合子群体相比，基因敲除动物还表现出社交行为减少和运动活动增加。通过免疫印迹法在死后脑组织中证实了突触素II基因的完全敲除。总之，这些结果证实突触素II基因敲除小鼠表现出与已建立的精神分裂症临床前动物模型相似的行为内表型，并支持突触素II表达异常可能在精神分裂症潜在病理生理机制中起因果作用的观点。
