Effect of overexpression of superoxide dismutase 1 mutant genes G41S and G41D on cognitive behavior in medial prefrontal cortex of mice / 中华行为医学与脑科学杂志

ABSTRACT

Objective:To investigate the effects of superoxide dismutase 1 (SOD1) mutations G41D and G41S on the cognitive behavior of mice.Methods:The recombinant adeno-associated virus (rAAV) which overexpressed human SOD1WT, SOD1G41S, SOD1G41D and the blank virus without the target gene were constructed, then they were stereotaxic injected into mice bilateral medial prefrontal cortex (mPFC) area respectively.According to the difference of injected virus, they were divided into CONTROL group, SOD1WT group, SOD1G41S group and SOD1G41D group ( n=16 in each group). One month later, open field test, Y-maze spontaneous alternation experiment, three box social interaction experiment and trace fear conditioning test were conducted to observe the effect of mutant gene on cognitive behavior of mice. Results:In the open field test, the movement distance of SOD1WT group((39.67±6.04)m)was significantly higher than that of SOD1G41D group((28.47±6.92)m, P=0.034). In the Y-maze spontaneous alternations experiment, the number of arm entries and actual alternations of arm entries of SOD1WT group((40.56±10.12)times, (32.63±8.19)times)and SOD1G41S group((36.75±9.43)times, (29.06±8.32)times)were significantly higher than those of SOD1G41D group((24.50±11.30)times, (18.38±9.09)times, P<0.05). In the three-compartment social experiment, there was no statistical difference between the residence time of SOD1G41D group in the area containing mouse ((279.08±134.94) s) and the empty metal cage area ((218.54±125.63) s) ( t=1.313, P=0.199). SOD1WT group and SOD1G41S group showed no statistical difference in the residence time in the regions of the unfamiliar mouse 1((253.07±55.60)s, (253.20±57.61)s) and the unfamiliar mouse 2 ((243.44±55.33) s, (239.76±67.49) s) ( P>0.05), and SOD1WT group and SOD1G41S group presented new social barrier.In the test stage of trace fear condition task, the percentage of freezing time of SOD1G41S group was significantly higher than that of other experimental groups and CONTROL group ( P<0.05). Conclusion:SOD1G41S and SOD1G41D have significantly changed the cognitive behavior of mice, and the two types of mutations at the same site have significant differences in the cognitive behavior changes.