Effects of genistein-3'-sodium sulfonate on motor function and brain autophagy level in Parkinson disease model mice
Objective To explore the effects of genistein-3'-sodium sulfonate(GSS)on on motor function and brain autophagy levels in Parkinson disease(PD)model mice.Methods Forty C57BL/6J mice were randomly divided into control group,model group,low-dose GSS group(0.15 mg/kg),medium-dose GSS group(0.50 mg/kg)and high-dose GSS group(1.50 mg/kg),with 8 mice in each group.Mice in the model group and the high,medium,and low-dose GSS groups were injected intraperitoneally with 1-meth-yl-4-phenyl-1,2,3,6-tetrahydropyridine to establish the PD mouse model,then mice in high,medium and low-close GSS group were intraperitoneally injected with corresponding doses of GSS(once a day for 21 days).The mice in model group were injected with equal volume 0.9％sodium chloride solution(once a day for 21 days),while the control group mice were fed normally.After 21 days,the motor and cognitive abilities of mice were evaluated by gait analysis,open field test,rotarod test,and modified Y maze test.Western blot was used to detect the expression levels of LC3-Ⅱ and Beclin-1 proteins in the cerebral cortex and striatum tissues of mice.SPSS 26.0 software was used for data analysis.One-way ANOVA was used for normal distri-bution data comparison among multiple groups,and LSD test was used for further pairwise comparisons,while Kruskal-Wails H test was used for non normal distribution data comparison.Results(1)Gait analysis showed that there were statistically significant differences in the stride length of left forelimb,left hindlimb,right hindlimb(F=5.93,6.21,3.78,all P＜0.01)and regularity index(H=14.409,P＜0.01).The regularity index of the model group mice was lower than that of the control group(P＜0.05),and the regularity indexes of the low,medium,and high-dose GSS groups were all higher than that of the model group(all P＜0.05).(2)In the open field test,there were statistically significant differences in the total distance and speed of movement among the 5 groups(F=5.49,5.49,both P＜0.01).The total distance and speed of movement in the model group were both lower than those in the control group(both P＜0.05).The total distance and speed of movement in the medium-dose GSS group((2 395.57±319.35)cm,(7.98±1.06)cm/s)and high-dose GSS group((2 386.51±396.00)cm,(7.95±1.32)cm/s)were higher than those of the model group((1 863.31±278.96)cm,(6.21±0.93)cm/s)and the low-dose GSS group((1 956.90± 297.15)cm,(6.52±0.99)cm/s)(all P＜0.05).(3)In the rotarod test and modified Y maze test,there were significant differences in latency to fall and residence time among the 5 groups(F=58.41,9.90,both P＜0.01).The latency to fall and residence time of model group were lower than those of control group(both P＜0.05),while those in the medium-dose and high-dose GSS groups were higher than those in the model group and low-dose GSS group(all P＜0.05).(4)Western blot results showed that there were significant differences in the expression levels of LC3-Ⅱ/LC3-Ⅰ ratio(F=8.17,15.47,both P＜0.01)and Beclin-1 pro-tein(F=29.07,20.54,both P＜0.01)in cerebral cortex and striatum among the five groups.The LC3-Ⅱ/LC3-Ⅰ ratio and Beclin-1 protein levels in the cerebral cortex((0.51±0.14),(0.46±0.06))and striatum((0.58±0.09),(0.55±0.10))of the model group were lower than those in the control group(cerebral cortex:(1.00±0.10),(1.00±0.05),striatumm:(1.00±0.06),(1.00±0.25),all P＜0.01).The LC3-Ⅱ/LC3-Ⅰ ratio and Beclin-1 protein in the medium-dose GSS group were higher than those in the model group,low-dose and high-dose GSS groups in both cerebral cortex and striatum(all P＜0.05).The lev-el of Beclin-1 of cerebral cortex in model group was lower than those in various doses of GSS group(all P＜0.05).There were no statistically significant differences of Beclin-1 protein levels between the model group mice and various doses of GSS groups in striatum(all P＞0.05).Conclusion GSS can improve the motor and cognitive functions of PD model mice,and the mechanism may be related to the upregulation of autophag-ic activity in the cerebral cortex and striatum of mice.
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