Chronic brain neuritis is important for the pathogenesis and progression of Alzheimer's disease (AD). Overexpression of tumor necrosis factor-α (TNFα)-inducible protein 8-like 2 (TIPE2), a novel immunoregulatory protein, reverses cognitive dysfunction in APP/PS1 mice. However, the mRNA profile changes in TIPE2 overexpression APP/PS1 mice and the molecular mechanism of cognitive attenuation remain unknown. In this study, after the Y-maze testing the spatial learning of the APP/PS1 mice and the TIPE2 overexpression APP/PS1 mice, high-throughput sequencing was performed on hippocampus tissues for analysis of mRNA profiles. A total of 183 differentially expressed genes (DEGs) were detected, of which 36 were down-regulated and 147 were up-regulated. Then, the mRNA profiles of the APP/PS1 mice and the wild-type mice were analyzed. A total of 196 DEGs were detected, of which 105 were down-regulated and 91 were up-regulated in the APP/PS1 mice. A comprehensive comparison of the mouse mRNAs showed that 20 genes were differentially expressed in both groups, among which, 19 genes showed an altered expression in the APP/PS1 mice, and the expression was recovered in TIPE2 overexpression APP/PS1 mice. We selected seven genes from these 19 genes, including Ttr, Lepr, Angptl2, Otx2, Clic6, Clo4a3 and Wfdc, for high-throughput sequencing. The results showed that, compared to the wild-type mice, these 7 genes were significantly down-regulated in the hippocampus of APP/PS1 mice. The expressions of a selected list of DEGs between APP/PS1 mice and APP/PS1 + OE mice were validated by quantitative real-time RT-PCR (qRT-PCR), and the results were consistent with the sequencing analysis. Taken together, increased adeno-associated virus (AAV)-mediated TIPE2 overexpression in the hippocampus of APP/PS1 mice reversed cognitive dysfunction. Transcriptional sequencing and bioinformatics analysis indicate that the attenuation of cognitive deficits was attributed to the recovery of certain genes.

慢性脑神经炎对于阿尔茨海默氏病（AD）的发病机理和进展至关重要。肿瘤坏死因子-α（TNFα）诱导蛋白8样2（TIPE2），一种新型的免疫调节蛋白的过表达逆转APP / PS1小鼠的认知功能障碍。然而，TIPE2过表达APP / PS1小鼠中的mRNA谱变化和认知减退的分子机制仍然未知。在这项研究中，在通过Y迷宫测试APP / PS1小鼠和TIPE2过表达APP / PS1小鼠的空间学习之后，对海马组织进行了高通量测序，以分析mRNA谱。总共检测到183个差异表达基因（DEG），其中36个被下调，而147个被上调。然后，分析APP / PS1小鼠和野生型小鼠的mRNA谱。总共检测到196个DEG，其中APP / PS1小鼠中有105个下调，有91个上调。小鼠mRNA的全面比较显示，两组中有20个基因差异表达，其中有19个基因在APP / PS1小鼠中表达发生了改变，在TIPE2过表达的APP / PS1小鼠中表达得以恢复。我们从这19个基因中选择了7个基因，包括Ttr，Lepr，Angptl2，Otx2，Clic6，Clo4a3和Wfdc用于高通量测序。结果表明，与野生型小鼠相比，这7个基因在APP / PS1小鼠海马中显着下调。通过定量实时RT-PCR（qRT-PCR）验证了APP / PS1小鼠和APP / PS1 + OE小鼠之间DEG选定列表的表达，其结果与测序分析一致。综上所述，APP / PS1小鼠海马中腺相关病毒（AAV）介导的TIPE2过量表达逆转了认知功能障碍。转录测序和生物信息学分析表明，认知缺陷的减轻归因于某些基因的恢复。