Dihuang Yinzi Improves Cognitive Function of Mouse Model of Learning and Memory Impairments by Regulating Synaptic Plasticity via SIRT2
10.13422/j.cnki.syfjx.20241901
- VernacularTitle:地黄饮子通过SIRT2调节突触可塑性改善学习记忆障碍小鼠认知功能的作用
- Author:
Wenting WANG
1
;
Yangjing HAO
1
;
Wenna SU
1
;
Qinqing LI
1
;
Shifeng CHU
2
;
Junlong ZHANG
1
;
Wenbin HE
1
Author Information
1. Shanxi Key Laboratory of Chinese Medicine Encephalopathy，National International Joint Research Center for Molecular Chinese Medicine，Shanxi University of Chinese Medicine，Jinzhong 030619，China
2. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines，Institute of Materia Medica & Neuroscience Center，Chinese Academy of Medical Sciences and Peking Union Medical College，Beijing 100050，China
- Publication Type:Journal Article
- Keywords:
Dihuang Yinzi;
learning and memory impairments;
protein kinase A/cAMP response element-binding protein （PKA/CREB） signaling pathway;
silent information regulator 2 （SIRT2）;
synaptic plasticity
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(6):9-17
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effects of Dihuang Yinzi on the cognitive function in the mouse model of learning and memory impairments induced by scopolamine （SCOP） and explore the treatment mechanism. MethodsA mouse model of learning and memory impairment was induced by intraperitoneal injection of SCOP. Sixty male C57BL/6J mice were randomized into six groups： control （0.9% NaCl， n=10）， model （SCOP 1 mg·kg-1·d-1， n=10）， low-， medium-， and high-dose Dihuang Yinzi （SCOP 1 mg·kg-1·d-1 + Dihuang Yinzi 5.5， 11.0， and 22.0 g·kg-1·d-1， n=10）， and donepezil （SCOP 1 mg·kg-1·d-1 + donepezil 0.84 mg·kg-1·d-1， n=10）. Mice were administrated with corresponding drugs for 6 weeks. Modeling started in the 4th week， and mice in other groups except the control group were injected with SCOP intraperitoneally 40 min after daily gavage. Behavioral testing began in the 5th week， 30 min after modeling each day. The Morris water maze and novel object recognition tests were carried out to evaluate the spatial learning and memory function of mice. Nissl staining was employed to observe the survival of neurons and Nissl bodies in the hippocampal CA1 region. Western blot was employed to determine the protein levels of silent information regulator 2 （SIRT2）， α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid （AMPA） receptor 1 （GluA1）， protein kinase A （PKA）， cAMP response element-binding protein （CREB）， phosphorylated-CREB （p-CREB）， postsynaptic density protein 95 （PSD95）， growth-associated protein-43 （GAP-43）， and synaptophysin （SYN） in the hippocampus. Immunofluorescence was used to detect the expression of doublecortin （DCX） in the hippocampal dentate gyrus （DG） region. ResultsCompared with the control group， the model group showed impaired learning and memory （P<0.01）， obvious neuronal damage in the hippocampal CA1 region， a reduction in neuron survival （P<0.01）， a decrease in DCX expression in the hippocampal DG region （P<0.01）， down-regulated proteins levels of GluA1， PKA， p-CREB/CREB， PSD95， SYN， and GAP-43 in the hippocampal tissue （P<0.05， P<0.01）， and an up-regulated protein level of SIRT2 （P<0.01）. Compared with the model group， the medium- and high-dose Dihuang Yinzi groups and the donepezil group showed improvements in learning and memory （P<0.05， P<0.01）， while the low-， medium-， and high-dose Dihuang Yinzi groups and the donepezil group had increased neuron survival （P<0.05， P<0.01）. The medium-dose Dihuang Yinzi group and the donepezil group showed increased DCX expression （P<0.05， P<0.01）. The medium- and high-dose Dihuang Yinzi groups and the donepezil group showed up-regulation in the protein levels of GluA1， PKA， p-CREB/CREB， PSD95， SYN， and GAP-43 （P<0.05， P<0.01） and down-regulation in the protein level of SIRT2 （P<0.01）. ConclusionDihuang Yinzi can improve the cognitive function in the mouse model of learning and memory impairments induced by SCOP by inhibiting the upregulation of SIRT2， activating the PKA/CREB signaling pathway， improving synaptic plasticity， and reducing hippocampal neuronal damage.
