Tiaobu Xinshen Prescription Promotes the Synthesis of Synaptic Plasticity-Related Proteins in 5xFAD Transgenic Mice with Alzheimer's Disease by Activating the PI3K/Akt/mTOR Pathway
10.19378/j.issn.1003-9783.2024.08.010
- VernacularTitle:调补心肾方通过活化PI3K/Akt/mTOR通路促进阿尔茨海默病5xFAD转基因小鼠突触可塑性相关蛋白的合成
- Author:
Zhiying LIN
1
;
Minglong YAO
;
Guanyi ZHENG
Author Information
1. 福建医科大学附属协和医院,福建 福州 350001
- Keywords:
Alzheimer's Disease;
Tiaobu Xinshen Prescription;
PI3K/Akt/mTOR signaling pathway;
synaptic plasticity-related proteins;
cognitive dysfunction;
5xFAD transgenic mice
- From:
Traditional Chinese Drug Research & Clinical Pharmacology
2024;35(8):1191-1196
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and mechanism of Tiaobu Xinshen Prescription(Codonopsis Radix,Polygoni Multiflori Radix Praeparata,Lycii Fructus,Astragali Radix,etc.)on synaptic plasticity in 5xFAD transgenic mice with Alzheimer's disease(AD).Methods Eighteen 5-month-old male wild-type(WT)mice and 18 5xFAD transgenic mice were randomly divided into control group(0.9％NaCl),Tiaobu Xinshen Prescription group(granules,4.18 g·kg-1)and Aricept group(Donepezil Hydrochloride,0.625 mg·kg-1),with six mice in each group.According to the above groups,the rats were given intragastric administration once a day for 60 days.The ultrastructure of hippocampus in mice was observed by transmission electron microscopy.Western Blot was used to detect the protein expression levels of Synaptophsin,PSD-95,p-NMDAR1,NMDAR1,p-CaMKⅡa,CaMKⅡa,PI3K,p-Akt,Akt,p-mTOR and mTOR in mouse cortical tissue.Results Compared with the WT mice control group,the ultrastructure of synapses in the hippocampal CA1 region of the 5xFAD control group was irregular,the mitochondria was atrophied and reduced,the mitochondrial cristae was broken and disappeared,the synaptic membrane was irregularly and curved,the synaptic vesicles were reduced,and the postsynaptic density(PDS)was thinned or even broken.The protein expressions of Synaptophsin,PSD-95,p-NMDAR1/NMDAR1,p-CaMKⅡa/CaMKⅡa,PI3K,p-Akt/Akt and p-mTOR/mTOR in the cortex were significantly down-regulated(P<0.05).Compared with the mice in the 5xFAD control group,the ultrastructure of synapses in the hippocampal CA1 region of the mice in the Tiaobu Xinshen Prescription 5xFAD group was significantly changed,the number of mitochondria was increased,the number of synaptic vesicles was increased,the synaptic membrane was intact,and the postsynaptic density was thickened.The protein expressions of Synaptophsin,PSD-95,p-NMDAR1/NMDAR1,p-CaMKⅡa/CaMKⅡa,PI3K,p-Akt/Akt and p-mTOR/mTOR in the cortex were significantly up-regulated(P<0.05).Conclusion Tiaobu Xinshen Prescription may promote the synthesis of synaptic plasticity-related proteins by activating the PI3K/Akt/mTOR pathway,thereby improving the cognitive dysfunction of AD.
