Danggui Shaoyaosan Alleviates Cognitive Impairment by Regulating Ketone Body Metabolism and Glutamate/AMPAR Pathway
10.13422/j.cnki.syfjx.20260104
- VernacularTitle:基于酮体代谢-谷氨酸/AMPAR信号通路探讨当归芍药散改善认知障碍的作用及机制
- Author:
Shasha WANG
1
;
Xin WANG
1
;
Kexin GONG
1
;
Yi QIU
1
;
Yanzi YU
1
;
Jiaqun SUN
1
;
Wenxuan CHEN
1
;
Huifei WU
2
;
Weirong LI
1
Author Information
1. Science and Technology Innovation Center， Guangzhou University of Chinese Medicine， Guangzhou 510405， China
2. Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine， Zhongshan 614001， China
- Publication Type:Journal Article
- Keywords:
Danggui Shaoyaosan;
Alzheimer's disease;
ketone body;
energy metabolism;
glutamate/α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid receptor （AMPAR） pathway;
cognitive impairment
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(18):44-52
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate whether the effect of Danggui Shaoyaosan （DSS） on cognitive impairment is related to its promotion of ketone body metabolism in the brain and regulation of glutamate/α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid receptor （AMPAR） pathway. MethodsMale APP/PS1 mice were randomized into model， low-dose （3.2 g·kg-1） DSS， medium-dose （6.4 g·kg-1） DSS， high-dose （12.8 g·kg-1） DSS， ketogenic diet， and inhibitor （talampanel， 5 mg·kg-1） groups. C57BL/6J wild-type mice were selected as the normal group. The talampanel group was intragastrically administered for 2 consecutive weeks from the 6th week， and the other groups were continuously treated for 8 weeks before behavioral testing. The ultrastructure of synapses in hippocampal CA1 region was observed by transmission electron microscopy， and calcium/calmodulin-dependent kinase Ⅱ （CaMKⅡ） expression was detected by immunohistochemistry （IHC）. The levels of β-hydroxybutyrate （BHB） and lactic acid （LAC） were measured by biochemical kits， and those of glutamate （Glu）， glutamine （Gln）， γ-aminobutyric acid （GABA）， and synaptophysin （SYP） by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of glutamine synthetase （GS）， glutaminase （GLS）， glutamate decarboxylase （GAD）， CaMKⅡ， and AMPAR subunits GluA1 and GluA2 were quantified by Real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of GS， GLS， GAD， GluA1， and GluA2 by Western blot. ResultsCompared with the normal group， the model group exhibited decreased recognition index， spontaneous alternation rate， and residence time in the target quadrant （P<0.01）， increased escape latency and ratio of the time in the opposite side of the target quadrant to the time in the target quadrant （P<0.05， P<0.01）， damaged synaptic ultrastructure of hippocampal CA1 region， increased positive expression of CaMKⅡ， no significant difference in BHB level， elevated LAC and Glu levels （P<0.01）， declined SYP， Gln， and GABA levels （P<0.01）， downregulated mRNA and protein levels of GS， GAD， and GluA2 （P<0.05， P<0.01）， and upregulated mRNA and protein levels of GLS and GluA1 （P<0.05， P<0.01） and mRNA level of CaMKⅡ （P<0.01）. Compared with the model group， DSS intervention improved the behavioral indexes of mice （P<0.05， P<0.01）， enhanced the synaptic ultrastructure plasticity in hippocampal CA1 region， decreased the positive expression of CaMKⅡ， raised the BHB level （P<0.01）， reduced the LAC and Glu levels （P<0.01）， elevated the SYP， Gln， and GABA levels （P<0.01）， upregulated the mRNA and protein levels of GS， GAD， and GluA2， and downregulated the mRNA and protein levels of GLS and GluA1 （P<0.05， P<0.01） and the mRNA level of CaMKⅡ （P<0.01）. ConclusionDSS can improve the learning and memory and enhance the synaptic plasticity of APP/PS1 mice. Its neuroprotective effect is coupled with the promotion of ketone body formation and remodeling of brain energy metabolism， and is related to the regulation of glutamate/AMPAR pathway.
