Effect of saikosaponin A on depressive-like behaviors and hippocampal CREB protein expression in olfactory bulbectomized mice
10.3760/cma.j.cn371468-20240928-00447
- VernacularTitle:柴胡皂苷A对嗅球切除小鼠抑郁样行为及海马CREB蛋白表达的影响
- Author:
Maoyun YUAN
1
;
Jingmei SONG
1
;
Hangfang LOU
1
Author Information
1. 浙江中医药大学基础医学院，杭州 310053
- Publication Type:Journal Article
- Keywords:
Saikosaponin A;
Olfactory bulbectomy;
Depressive-like behaviors;
Cyclic adenosine monophosphate response element-binding protein
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2025;34(1):2-8
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of saikosaponin A on depressive-like behaviors and hippocampal cyclic adenosine monophosphate response element-binding(CREB) protein expression in olfactory bulbectomized mice.Methods:Totally thirty male SPF-grade C57BL/6J mice, six weeks old, were randomly divided into 3 groups ( n=10 in each group): the control group, the olfactory bulbectomy group, and the saikosaponin A group.Olfactory bulbectomy was performed to damage the olfactory bulbs in the mice of bulbectomy group and saikosaponin A group, while the mice of control group only had a cranial drill hole at the same coordinates without damaging the olfactory bulbs. Mice in saikosaponin A group were administered saikosaponin A solution (dose: 5 mg/kg) via gavage, while mice in the control and olfactory bulbectomy groups were given the same volume of 0.9% NaCl solution once a day for 21 days. The depressive-related behavioral changes of mice in each group were evaluated by open field test, tail suspension test, forced swimming test, and weight measurement. The expression of CREB in the hippocampus of mice were detected by Western blot. Graphpad prism 5 software was used for data analysis.The data comparison among the multiple groups was conducted by one-way ANOVA and further pairwise comparisons were conducted by Tukey test. Results:(1) The results of weight measurement showed that there was no significant difference in body weight among the three groups( F=0.468, P=0.631) on the day of the olfactory bulbectomy surgery, but there was a statistically significant difference in body weight among the three groups ( F=37.340, P<0.001) on the 28th day after the olfactory bulbectomy.The body weight of mice in the olfactory bulbectomy group was lower than that of the control group ((24.09±1.01) g, (27.22±0.58)g)( P<0.05). The body weight of mice in the saikosaponin A group((26.23±0.83)g) was higher than that of the olfactory bulbectomy group( P<0.05). There was a statistically significant difference in body weight differences among the three groups of mice ( F=48.180, P<0.001). The body weight difference of mice in the olfactory bulbectomy group was lower than that of the control group ((2.34±0.96) g, (5.57±0.72) g) ( P<0.05). The body weight difference of mice in the saikosaponin A group was higher than that of the olfactory bulbectomy group ((4.74±0.56) g, (2.34±0.96) g) ( P<0.05).(2) The results of the open field test showed that there were statistically significant differences in the central area residence time and total activity distance in mice among the three groups ( F=27.03, 10.98, both P<0.001). The central area residence time ((13.87±4.59) s) and total activity distance ((35.67±4.88) m) of mice in the olfactory bulbectomy group were both less than those of the control group ((27.44±2.76) s, (59.02±16.21) m) (both P<0.05).The central area residence time ((21.77±4.78) s) and total activity distance ((52.33±10.41) m) of mice in the saikosaponin A group were both higher than those of the olfactory bulbectomy group(both P<0.05).(3) The results of tail suspension test showed that there was a statistically significant difference in immobility time among the three groups ( F=74.57, P<0.001). The immobility time of mice in the olfactory bulbectomy group was longer than that of the control group ((148.20±8.84)s, (97.89±8.64)s) ( P<0.05). The immobility time of mice in the saikosaponin A group((135.70±11.09)s) was less than that of the olfactory bulbectomy group( P<0.05). (4) The results of forced swimming test showed that there was a significant difference in immobility time among the three groups ( F=51.73, P<0.001). The immobility time of mice in the olfactory bulbectomy group was longer than that of the control group ((61.39±5.20) s, (40.80±4.30) s) ( P<0.05).The immobility time of mice in the saikosaponin A group((53.52±4.13)s) was less than that of the olfactory bulbectomy group( P<0.05). (5) The results of Western blot showed that there was a significant difference in hippocampal CREB protein expression among the three groups ( F=13.32, P<0.001).Compared with the control group, hippocampal CREB protein expression of mice in the olfactory bulbectomy group was significantly down-regulated(0.51±0.15, 1.45±0.61) ( P<0.05).Compared with the olfactory bulbectomy group, hippocampal CREB protein expression in the saikosaponin A group(0.97±0.09) was up-regulated( P<0.05). Conclusion:Saikosaponin A can significantly alleviate the depressive-like behaviors in olfactory bulbectomized mice, and its mechanism may be related to the up-regulation of CREB protein expression in the hippocampus.
