Effects of deubiquitinase UCHL5 on spatial learning and memory ablity in mice

GAO Qiaohui; JIAO Shengyuan; GUO Li; WANG Jianyu; DA Fei; LIU Junye

doi:10.13276/j.issn.2097-1656.2024.05.006

Abstract：Objective To investigate the effect of ubiquitin carboxyl-terminal hydrolyse L5(UCHL5)on spatial learning and memory function by UCHL5 knockout mouse models.Methods UCHL5 brain conditioned knockout mice were constructed using CRISPR/Cas9 technology.A total of 16 UCHL5 brain knockout mice and 16 wild-type mice aged 4 months and above were selected.Tamoxifen was injected intraperitoneally for 5 consecutive times,once every other day.After successful modeling,UCHL5 expression level in mouse brain tissue was identified by Western blotting method.Morris water maze experiment was used to detect the effect of UCHL5 knockout on the spatial learning and memory ability of mice.Results Western blotting experiments showed that the expression of UCHL5 protein was lost in the brain tissue of knockout mice.UCHL5 knockout affected the spatial learning and memory ability of mice.The results of place navigation test showed that the average latency of UCHL5 knockout mice was longer than that of wild-type mice,and the average latency was prolonged on the first and third day of training,but the difference was not statistically significant(P=0.403,P=0.067).The average latency was significantly prolonged on the 2nd,4th and 5th day of training(all P＜0.05).The results of space exploration experiments showed that the time ratio of UCHL5 knockout mice in the target quadrant was significantly lower than that of wild-type mice[(7.71±0.81)％vs(9.60±0.51)％,P=0.042].The total swimming distance of UCHL5 knockout mice was higher than that of wild-type mice[(7 500.92±14.35)cm vs(6 034.48±17.10)cm,P＜0.001].Conclusion UCHL5 expression level affects the spatial learning and memory ability of mice.