Abstract: Objective To investigate the impact of annexin A1 (AnxA1) gene deficiency on cognitive function of mice and its underlying molecular mechanisms. Methods AnxA1-knockout (AnxA1-KO) mouse model constructed using CRISPR/Cas9 gene editing technology; Spatial cognition and memory functions were assessed using the Morris water maze, open field test, novel object recognition, and Y-maze test. The impact of AnxA1 knockdown on the proliferation and migration capability of mouse hippocampal neuronal cell line HT22 was evaluated using Western blot, real-time cell analysis (RTCA), and Transwell assays. The relationship between AnxA1 and the p38 MAPK signaling pathway was also examined. Results PCR genotyping confirmed successful generation of AnxA1-KO mice. Compared with wild-type (WT) mice, AnxA1-KO mice exhibited significantly decreased spatial exploration ability, spontaneous alternation rate, novel object discrimination index, and time spent in the safe zone(P＜0.05). After AnxA1 knockdown, the proliferation and migration ability of HT22 cells were significantly lower than those of the control group (P＜0.05). Furthermore, AnxA1 knockdown significantly activated the p38 MAPK signaling pathway, leading to increased levels of phosphorylated p38 (p-p38). Conclusions The deficiency of AnxA1 may lead to cognitive impairment of mice by activating the p38 signaling pathway, which subsequently inhibits neuronal proliferation and migration.

Key words: annexin A1(AnxA1), CRISPR/Cas9, mouse hippocampal neuron, cognitive function