脑老化通常会导致学习能力的下降与部分记忆的丧失，极大地影响了老年人的生活质量，但因其涉及的细胞及分子机制仍未阐明，预防和治疗的措施远不能满足当今老龄化社会的需求。本课题组前期发现电压门控性钠离子通道2型beta 亚基(SCN2B) knockdown可以显著改善老年转基因小鼠海马依赖性的空间认知记忆并且有利于易化海马神经元的长时程电势，但其作用的分子机制尚未阐明。我们推测SCN2B在脑老化引发的认知功能减退中发挥重要作用，其机制可能为与Nav1.6相互作用并调节老年动物功能脑区APP和Aβ。为了证明我们的推测，本课题组拟通过制作APP/SCN2B转基因动物模型，运用多种细胞模型，通过认知功能检测、神经电生理、形态学、分子生物学等手段检测SCN2B在APP加工处理及Aβ产生过程中的作用、对Nav1.6的调节作用，探讨APP在SCN2B介导的认知功能改善中的作用，为临床治疗脑老化提供分子靶点。

Brain senescence often leads to learning deficits and memory deterioration. However, the underlying cellular and molecular mechanisms have not been elucidated. Current clinical progress for the prevention and treatment of brain senescence is also far from being satisfactory. Our previous data revealed that a downregulation of SCN2B in SCN2B-knockdown mice resulted in improving the hippocampus-dependent spatial recognition memory and facilitating hippocampal long-term potentiation. But, the mechanisms underlying is still unknown. We propose that SCN2B could play an important role in the aging-related cognitive deterioration, which is associated with the regulations of APP and Aβ in aged mice by Nav1.6 regulation. Therefore, in the present study, by using recognize behavior evaluation, electroneurophysiology, morphological and molecular biology assessments, we will determine: 1) roles of SCN2B in APP processing and Aβ production; 2) roles of SCN2B in Nav1.6 regulation; 3) roles of APP in SCN2B-induced cognitive improvement. The present study could provide the potential strategy of candidate target to develop anti-senescence drugs for the treatment of brain aging.