精神分裂症患者老化加速，寿命显著低于正常人群。精神分裂症大脑的老化有着比较独特的病理进程，然而其内在的分子和神经生物学机制很不清楚。缺乏有效和公认的动物模型制约了精神分裂症脑老化机制的研究。一般认为，神经突触的功能紊乱是导致精神分裂症的神经生物学机制。那么，神经突触紊乱是否也是精神分裂症脑老化的直接原因？通过修正神经突触的紊乱，是否可以改善精神分裂症脑老化的进程？申请人发现TARP g-8突变降低AMPA受体介导的兴奋性突触后电流（EPSC）并损伤长时程突触增强（LTP）。而且TARP g-8敲除小鼠具有精神分裂症样行为表型，并表现出加速衰老的迹象。因此，申请人将以TARP g-8敲除小鼠作为精神分裂症模型，利用电生理、分子生物学和行为学方法研究精神分裂症特异的脑加速老化的机理。

Schizophrenia has speeded aging, leading to significant reduction of lifespan. The brain aging of schizophrenia is dramatic and likely has unique mechanisms. However, our understanding of the mechanisms underlining schizophrenia brain aging is very limited, due to lacking of appropriate animal models. It is generally recognized that synaptic dysfunction causes schizophrenia. Is synaptic dysfunction also the direct cause of schizophrenia-related brain aging? If so, would correction of schizophrenia synaptic dysregulation ameliorate the brain aging? We found that TARP g-8 (CACNG8) mutation leads to decrease of AMPA receptor mediated EPSC and impairs long-term potentiation. Moreover, the TARP g-8 knockout mice display schizophrenia-like behaviors and speeded aging. Therefore, we would propose to study the schizophrenia-related brain aging mechanisms using TARP g-8 knockout mouse model.