双相情感障碍易感基因Trank1的功能研究

双相障碍是一类重性精神疾病，从遗传学入手筛选其风险基因并解析风险基因的神经生物学功能及其参与疾病发生的分子机制，可为双相障碍的临床诊疗提供重要基础数据。Trank1是通过全基因组关联分析鉴定出与双相障碍发生最为相关的遗传风险基因之一，但是到目前为止，该基因的生物学功能仍知之甚少。我们在前期工作中验证了Trank1是中国人群双相障碍的重要遗传风险基因，并首次通过实验揭示了Trank1对突触形成具有影响，然而，Trank1更深层次的神经生物学功能及其参与双相障碍发生的病理机制还需深入研究。在本项目中，我们将依赖于Trank1转基因及基因敲除小鼠，分析该基因对模式动物行为学及突触功能的影响；我们还将在体外及体内模型中解析Trank1影响突触表型的分子机制；此外，我们还将分析Trank1与双相障碍临床病征的相关性及潜在应用价值。上述研究结果有利于全面理解双相障碍发生的病理机制。

Bipolar disorder (BD) is a severe psychiatric disorder. Identifying risk genes of bipolar disorder by genetic analysis and understanding the neuronal functions of the candidate risk genes can provide essential data for the clinical investigation of the disease. Although Trank1 was characterized as the lead risk gene of bipolar disorder by genome-wide association studies (GWAS), the neuronal function of TRANK1 in bipolar disorder is still unclear so far. In our recent study, we have demonstrated that Trank1 was a risk gene of bipolar disorder in East Asian population and abnormal expression of Trank1 could affect synapse formation, however, the detailed neuronal functions of TRANK1 and the role of Trank1 in the development of bipolar disorder requires further investigation. In this study, we intend to understand if Trank1 can affect the behavior test of mice by employing in vivo models; we will also investigate how Trank1 can affect the formation of synapse and resolve the underling mechanisms; in addition, we plan to analyze the correlation between Trank1 expressions in peripheral circulation and status of bipolar disorder and explore the clinical application value of peripheral circulating Trank1. These studies will provide hints on the molecular mechanisms underlying the susceptibility of biopolar disorder conferred by Trank1.