AnxA5基因缺失降低小鼠认知机制研究OA

Objective To investigate the regulatory effect and molecular mechanism of annexin A5(AnxA5)gene on cognitive function in mice.Methods AnxA5 gene knockout(AnxA5-/-)mice were constructed by CRISPR/Cas9 technology.The regulatory effect of AnxA5 on cognitive function in mice was verified by Morris water maze,Y maze and novel object recognition tests.Western blot,qPCR,immunofluorescence,real-time cell analysis(RTCA)and other method were used to detect the effects of AnxA5 deletion on the proliferation and morphology of mouse hippocampal neurons,and to explore its regulatory mechanism.APP/PS1 double transgenic mice were used as positive controls for Alzheimer's disease.Results Compared with wild-type(WT)C57BL/6 mice,the cognitive function of AnxA5-/-mice was significantly reduced(P＜0.05).After interfering with the expression of AnxA5 gene in HT-22 cells,the cell proliferation ability was significantly weakened(P＜0.05),the cell morphology was irregular,and AnxA5 deletion could activate the P65 signaling pathway.Conclusions AnxA5 gene deletion can up-regulate the expression level of inflammatory factors by activating the P65 pathway,thereby damaging mouse hippocampal neurons and ultimately leading to cognitive impairment in mice.