Identification of drug target for novel antipsychotics based on proteomic approach

反复给药苯环利定（PCP）已知会在小鼠中产生精神分裂症样症状。为了检测PCP反复处理后小鼠前额皮质（PFC）蛋白表达的变化，我们使用2D-DIGE进行了蛋白质组学分析。蛋白质组学分析显示，经PCP反复治疗后，PFC中14-3-3蛋白θ的表达水平发生了显著变化。在一项新的物体识别测试中，将14-3-3蛋白抑制剂微量注射到PFC会导致记忆障碍。上述结果提示PFC 14-3-3蛋白θ功能障碍可能参与反复pcp治疗小鼠精神分裂症样症状的分子机制。

Repeated administration of phencyclidine (PCP) has known to produces schizophrenic-like symptoms in mice. To examine the changes in protein expression after repeated PCP treatment in the prefrontal cortex (PFC) of mice, we performed proteomic analysis by using 2D-DIGE. Proteomic analysis reveals that the remarkable change in the expression levels of 14-3-3 protein θ was observed in the PFC after repeated treatment with PCP. The signals was localized to cells positive for S100, a marker of glial cells, in the PFC. Microinjection of 14-3-3 protein inhibitor into the PFC lead to memory impairment in a novel object recognition test. These results suggest that dysfunction of 14-3-3 protein θ in the PFC may be involved in the molecular mechanisms underlying the schizophrenic-like symptoms in repeated PCP-treated mice.