Mechanism of Kaixinsan on Learning and Memory Ability and Synaptic Function of APP/PS1 Mice
10.13422/j.cnki.syfjx.20212036
- VernacularTitle:开心散对APP/PS1小鼠学习记忆能力和突触功能的机制
- Author:
Yu-min XU
1
;
Xiao-ming SHEN
1
;
Rui LAN
1
;
Shi-rui ZHU
1
;
Jie ZHANG
1
;
Fang-mei LU
2
;
Bao-qi WANG
2
;
Yun-zhi MA
1
Author Information
1. The First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450000，China
2. Henan University of Chinese Medicine，Zhengzhou 450000，China
- Publication Type:Research Article
- Keywords:
Kaixinsan;
Alzheimer's disease;
synaptic plasticity-related proteins;
oxidative stress;
cholinergic neurotransmitter;
learning and memory ability
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(20):15-22
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the underlying protective mechanism of Kaixinsan on learning， memory， and synaptic function in APP/PS1 mice. Method:Sixty APP/PS1 mice were randomly divided into a model group， a donepezil （2 mg·kg-1·d-1） group， and low- （0.7 g·kg-1·d-1）， medium- （1.4 g·kg-1·d-1）， and high-dose （2.8 g·kg-1·d-1） Kaixinsan groups， and the wild-type mice of the same age in the same litter were assigned to the normal group， with 12 mice in each group. After continuous intragastric administration for two months， the Morris water maze experiment was performed. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The colorimetric assay was used to detect serum content of acetylcholine （ACh）， choline acetyltransferase （ChAT）， acetylcholinesterase （AChE）， and levels of hippocampal reactive oxygen species （ROS）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Real-time fluorescence-based quantitative polymerase chain reaction （Real- time PCR） was used to detect the mRNA expression of hippocampal brain-derived neurotrophic factor （BDNF）， beta-nerve growth factor （NGFB）， discs large homolog (DLG)2， DLG4， and synaptophysin （SYP）. Result:Compared with the normal group， the model group showed prolonged escape latency， reduced number of crossing platforms， shortened stay in the target quadrant （P<0.01）， decreased number of mitochondria with different shapes and irregular arrangement， some swollen and deformed mitochondria with broken mitochondrial cristae， endolysis， and cytoplasm vacuole， and more cell debris. Additionally， the model group also displayed reduced serum levels of ACh and ChAT， increased AChE （P<0.01）， elevated hippocampal ROS and MDA （P<0.05，P<0.01）， declining SOD and GSH-Px （P<0.01）， and diminished hippocampal BDNF， NGFB， DLG2， DLG4， and SYP mRNA levels （P<0.05，P<0.01）. Compared with the model group， the donepezil group， and the medium- and high-dose Kaixinsan groups showed shortened escape latency， increased number of crossing platforms， prolonged stay in the target quadrant （P<0.05，P<0.01）， improved mitochondrial damage with a regular shape （mainly oval shape）， relieved mitochondrial swelling and deformation， and clear mitochondrial cristae. Furthermore， the donepezil group， and the medium- and high-dose Kaixinsan groups also exhibited increased serum ACh and ChAT levels （P<0.05，P<0.01）， blunted AChE activity （P<0.05）， reduced hippocampal ROS level （P<0.05，P<0.01）， declining MDA level （P<0.05）， potentiated SOD and GSH-Px activities， and up-regulated hippocampal BDNF， NGFB， DLG2， DLG4， and SYP mRNA levels （P<0.05，P<0.01）. In the low-dose Kaixinsan group， the stay time in the target quadrant was prolonged and the expression of hippocampal SYP mRNA was elevated significantly （P<0.05）. There was no statistical difference in swimming speed between the groups. Conclusion:Kaixinsan can improve the learning and memory ability of APP/PS1 mice by increasing the expression of synaptic plasticity-related proteins， reducing the ultrastructural damage to hippocampal neurons， resisting oxidative stress， and regulating cholinergic neurotransmitters， thereby exerting neuroprotective effects.
