最近研究显示精神分裂症患者血清中存在N-甲基-D-天冬氨酸（NMDA）受体亚单位GluN1抗体和GluN2B抗体，GluN1抗体引起小鼠自发活动能力下降和前脉冲抑制（PPI）损害，表明GluN1抗体与认知损害相关，但其在精神分裂症认知损害中的具体作用机制尚未清楚。具有NMDA受体抗体的脑炎患者与精神分裂症患者的精神症状相似，这类患者的GluN1抗体通过内吞作用下调NMDA受体表达及扰乱NMDA受体与CaMKⅡ相互作用引起谷氨酸能神经传递异常和突触可塑性损害而诱发认知损害。我们假设NMDA受体抗体在精神分裂症中可能具有类似作用机制。本项目主要研究GluN1抗体和GluN2B抗体在精神分裂症认知损害中的作用及机制，阐明这两个抗体对NMDA受体表达影响及NMDA受体表达改变对小鼠认知功能的影响，并阐明引起NMDA受体表达改变的信号通路，以及干预NMDA受体及其信号通路对小鼠认知损害的作用。

Recent clinical studies showed that N-methyl-D-aspartate (NMDA) receptor antibodies, like anti-GluN1 antibody and anti-GluN2B antibody, were found in patients with schizophrenia. GluN1 antibody led to reductions in spontaneous open-field activity and impairments in pre-pulse inhibition (PPI) in mice. However, the mechanism of anti-NMDA receptor antibody in cognition impairments of schizophrenia was unclear. Anti-NMDA receptor encephalitis patients show psychotic symptoms similar to schizophrenia. Previous studies showed that GluN1 antibody of anti-NMDA receptor encephalitis patients induced reduced expression of NMDA receptor by receptor internalization and disrupted cross-talk between NMDA receptor and CaMKⅡ, which lead to glutamatergic dysregulation, synaptic plasticity impairment and cognitive impairment. We hypothesized that NMDA receptor antibodies may have a similar mechanism for cognitive impairments in schizophrenia. Our study aims to clarify the role and mechanism of GluN1 antibody and GluN2B antibody in the cognitive impairments induced by schizophrenia. We will detect the effect of NMDA receptor antibodies on expression of NMDA receptor and the effect of altered NMDA receptor expression on cognitive function in mice. We will also demonstrate the signaling pathway related to changes of NMDA receptor expression and the effect of interfering NMDA receptor and the signaling pathway on cognitive impairments in mice.