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Outline
To explore the mechanism of soy isoflavones (SIF) in improving memory in aging ovariectomized rats.
Forty 8-week-old SD female rats were randomly assigned to the sham control (CON), aging combined with ovariectomy(OVX/D-Gal), 160 mg/kg SIF (SIF) and 0.8 mg/kg estradiol replacement therapy (ERT). Except for the CON group, rats in other groups underwent bilateral ovariectomy combined with intraperitoneal injection of D-galactose (100 mg/kg·d) for 12 weeks.After the intervention, memory was assessed using the shuttle box test. Transmission electron microscopy was used to observe the synaptic ultrastructure of hippocampal neurons. The protein P53, PSD-95, GluA1, P38 and the phosph-P38 (p-P38)expressions were measured by Western blot. The levels of TNF-α and estradiol were detected by ELISA. One-way ANOVA method was used to analyze the overall differences. LSD method was used to analyze the pairwise comparison between groups with homogeneous variance, and Dunnett’s test was used to analyze those with uneven variance, with α=0.05.
Significant differences were observed among the groups in avoidance latency time (ALT), active avoidance response rate (AAR),synaptic interface curvature (SIC), synaptic cleft width (SCW), postsynaptic density (PSD) thickness, serum E2 levels, protein expressions of P53, PSD-95, GluA1 and P38 in the hippocampus, and p-P38/P38 (F-value=10.905, P-value<0.010; F-value=9.825, P-value<0.010; F-value=8.027, P-value<0.010; F-value=124.228, P-value<0.001; F-value=24.9810, P-value<0.001; F-value=16.410, P-value<0.001; F-value=5.667, P-value<0.050; F-value=6.091, P-value<0.050; F-value=8.766, P-value<0.050; F-value=25.218, P-value<0.001; F-value=19.014, P-value<0.001). Compared with CON group, rats in the OVX/D-Gal group exhibited significantly reduced serum E2 and increased hippocampal P53, accompanied by prolonged ALT and decreased AAR. The SIC and PSD thickness declined, and the SCW widened. The level of TNF-α and the ratio of p-P38/P38 in the hippocampus increased, while the protein expressions of P38, PSD-95 and GluA1 were decreased (all P-value<0.050).In the SIF group, there was no significant change in serum E2 level compared to the OVX/D-Gal group, while P53 expression was decreased. The ALT shortened and the AAR increased. Besides, higher SIC, increased PSD thickness, and narrower SCW were observed in the SIF group. The level of TNF-α and the ratio of p-P38/P38 in the hippocampus declined, while the protein expressions of PSD-95, GluA1 and P38 increased (all P-value<0.050).
SIF can improve the memory ability of aging rats with ovariectomy, which may be related to the enhancement of synaptic plasticity through inhibiting TNF-α and its downstream P38MAPK, thereby increasing GluA1 expression.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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