Effects of Huanshaodan on learning and memory impairment and p38MAPK/ERK1/2 signaling pathway in Alzheimer's disease model mice
10.3760/cma.j.cn371468-20240604-00259
- VernacularTitle:还少丹对阿尔茨海默病模型小鼠学习记忆障碍及p38MAPK/ERK1/2信号通路的影响
- Author:
Zhengda YIN
1
;
Peiwei CONG
1
;
Danyu ZHAO
1
;
Lu REN
1
;
Xu WANG
1
Author Information
1. 辽宁中医药大学中西医结合学院，沈阳 110847
- Publication Type:Journal Article
- Keywords:
Huanshaodan;
Alzheimer's disease;
Neuroinflammatory response;
p38 mitogen-activated protein kinase;
Extracellular signal-regulated kinase 1/2
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2025;34(2):104-110
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of Huanshaodan on improving learning and memory impairment in a mouse model of Alzheimer's disease (AD) which was named with senescence accelerated mouse-prone 8(SAMP8), as well as the neuroinflammatory response mechanisms mediated by the p38 mitogen activated protein kinase (p38MAPK) and extracellular signal regulated protein kinase 1/2 (ERK1/2) signaling pathways.Methods:Seven-month-old SPF grade male SAMP8 mice were randomly assigned into three groups(6 mice in each group) using a random number table: model group, low-dose Huanshaodan group(1.17g/kg, twice daily via gavage), and high-dose Huanshaodan group(2.34g/kg, twice daily via gavage).Weight-matched seven-month-old male mice with anti-rapid aging traits(senescence-accelerated mouse-resistant 1, SAMR1)were designated as the normal control group( n=6).The mice in control group and the model group received 0.9% NaCl via gavage twice daily.All mice underwent continuous interventions for 28 days.The learning and memory abilities were assessed by Morris water maze.Immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP) and ionized calcium-binding adaptor molecule-1(Iba1) as markers for astrocytes and microglial cells in the hippocampus, respectively.ELISA was used to measure pro-inflammatory cytokines interleukin-6(IL-6), interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in hippocampal tissue.Western blot was used for analyzing the expression levels of pro-inflammatory enzymes, inducible nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2), as well as phosphorylated levels of ERK1/2 and p38MAPK in hippocampal tissue.Data were statistically analyzed using SPSS 20.0.The repeated measures analysis of variance or one-way analysis of variance was used for multi groups comparison. Results:Morris water maze test results indicated interactions between time and group in the escape latencies of the four groups of mice( F=3.787, P<0.05).From the 5th to 6th day, the escape latencies of the low- and high-dose Huanshaodan groups were lower than those of the model group(both P<0.05).On the 4th to 6th day, the escape latencies of the high-dose Huanshaodan group were lower than those of the low-dose group(all P<0.05).Significant differences were observed in the residence time in the target quadrant and the number of crossing the platform among the four groups of mice( F=8.587, 12.633, both P<0.05).The residence time in the target quadrant of the model group((17.8±3.4)s) and the number of crossing the platform((1.6±0.6)times)were less than those of the control group((40.6±3.7)s, (4.6±0.6)times) and high-dose Huanshaodan group(31.8±4.0)s, (2.8±0.8)times), all P<0.05).Western blot results indicated significant differences in the expression of iNOS, COX-2, p-p38MAPK/p38MAPK, and p-ERK1/2/ERK1/2 in the hippocampal tissues of the four groups of mice( F=207.516, 10.627, 108.497, 34.330, all P<0.05) and the indexes in model group were all higher than those of control group and high-dose Huanshaodan group(all P<0.05).ELISA results revealed significant differences in the levels of IL-6, TNF-α and IL-1β in the serum of the four groups of mice( F=66.790, 82.424, 42.919, all P<0.05), and the indexes of model group were higher than those of the other three groups(all P<0.05).Immunofluorescence results showed significant differences in the relative fluorescence intensity of GFAP and Iba1 in the hippocampal tissues of the four groups of mice( F=20.269, 56.437, both P<0.05).The relative fluorescence intensity values of GFAP and Iba1 in the hippocampal tissues of the high-dose Huanshaodan group were lower than those of the model group(both P<0.05), while the expression level of Iba1 in high-dose group was lower than that in the low-dose group( P<0.05). Conclusion:High-dose Haunshaodan may inhibit the activation of hippocampal glial cells by blocking the p38MAPK and ERK1/2 pathways, reducing neuroinflammation, then improving learning and memory disorders in SAMP8 mice.
