Yigong San improves learning and memory functions of APP/PS1 transgenic mice by regulating brain fluid metabolism
10.12122/j.issn.1673-4254.2024.10.20
- VernacularTitle:异功散通过调控脑水液代谢改善APP/PS1转基因小鼠的学习记忆能力
- Author:
Jing ZENG
1
;
Lei HUA
;
Yong YANG
;
Xiaomei ZHANG
;
Jiangping WEI
;
Lisheng LI
Author Information
1. 中药新药创制川渝共建重点实验室;国家中医药管理局中药化学三级实验室,重庆市中药研究院,重庆 400065;遵义医科大学 基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,贵州 遵义 563000;遵义医科大学 贵州省基础药理重点实验室//药学院药理学教研室,贵州 遵义 563000
- Keywords:
Yigong San;
dementia;
brain fluid metabolism system;
APP/PS1 mice;
aquaporin-4
- From:
Journal of Southern Medical University
2024;44(10):2015-2023
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism by which Yigong San(YGS)improves learning and memory abilities of APP/PS1 transgenic mice in light of cerebral fluid metabolism regulation.Methods Three-month-old male APP/PS1 transgenic mice and wild-type C57BL/6 mice were both randomized into control group,model group,donepezil(1.67 mg/kg)group,and YGS(7.5 g/kg)group and received the corresponding treatments via gavage once daily for one month.After the treatments,the mice were assessed for learning and memory functions using Morris water maze test and examined for hippocampal and cortical pathologies and amyloid plaques using HE,immunohistochemical and thioflavin S staining;ELISA and Evans blue method were used for detecting Aβ1-40 and Aβ1-42 levels in the brain tissue and serum and assessing blood-brain barrier(BBB)integrity.Immunofluorescence colocalization was used to investigate AQP4 polarization on astrocytes.Western blotting was performed to detect the expressions of VE-cadherin,ZO-1,occludin,β-amyloid precursor protein(APP),BACE1,insulin-degrading enzyme(IDE),LRP1,RAGE,and AQP4 proteins.Results Compared with the control mice,APP/PS1 mice showed significant impairment of learning and memory abilities,increased degeneration or necrosis of hippocampal and cortical neurons,pathological scores,Aβ-positive plaques,elevated Aβ1-40 and Aβ1-42 levels in the brain tissue and serum,increased BBB permeability,upregulated RAGE expression,lowered expressions of VE-cadherin,LRP1,ZO-1,occludin,and AQP4 proteins,and reduced AQP4-expressing GFAP-positive cells.YGS treatment significantly improved the performance of the transgenic mice in Morris water maze test,reduced hippocampal and cortical pathologies and Aβ-positive plaques,and ameliorated the abnormal changes in Aβ1-40 and Aβ1-42 levels,BBB permeability,protein expressions of RAGE,VE-cadherin,LRP1,ZO-1,occludin and AQP4,and the number of AQP4-expressing GFAP-positive cells.Conclusion YGS improves learning and memory changes in APP/PS1 mice by ameliorating neuronal damage and Aβ pathology in the brain and regulating brain fluid metabolism.
