“Zhisanzhen” Regulates Lipid Metabolism in AD Mice and Enhances Synaptic Network Function

摘要

Objective: Alzheimer's disease(AD) involves aberrant lipid metabolism. Zhisanzhen(ZSZ) acupuncture is known to regulate lipid metabolism. This study investigates the effects of ZSZ on lipid metabolism and synaptic function in AD mice. Methods: Triple-transgenic(APP/PS1/TAU) AD model mice(28 weeks old) were divided into AD model control, ZSZ treatment, and the non-acupoint control group. The ZSZ treatment group received acupuncture at the Zusanli, Neiguan, and Sanyinjiao acupoints, with electricity stimulation until the sensation was obtained. The treatment was given once a day, 10 minutes after acupuncture. The sham acupuncture group received acupuncture around the Zusanli, Neiguan, and Sanyinjiao. After each group was intervened for 4 weeks, the body weight and blood lipids of the mice were observed. Liver tissues and hippocampal tissues were taken for transcription and lipidome analysis. At the same time, field potential detection was performed on the CA3-CA1 area of the mice hippocampus. The input-output(I-O) curve, doublepulse facilitation(PPF), and long-term potentiation(LTP) were used to clarify the impact on the synaptic network transmission function. Results: After 4 weeks of intervention, the body weight of AD mice in the ZSZ and sham acupuncture groups decreased to a certain extent(P>0.05); the blood triglyceride(TG) levels of mice in both groups decreased, with more significant decreases in the ZSZ group(P<0.01) compared to the sham acupuncture group(P<0.01); the blood total cholesterol(TC) levels in the ZSZ group decreased significantly(P<0.05); in the hippocampal tissue, there were 112 significantly down-regulated genes and 19 significantly up-regulated genes, mainly enriched in neurodegenerative diseases, amyotrophic lateral sclerosis, PI3K-Akt and other signaling pathways. In the liver tissue, there are 18 down-regulated genes and 29 up-regulated genes. The differentially expressed genes are mainly enriched in metabolic, thermogenesis, and neurodegenerative disease pathways. Liver oil red staining shows that ZSZ can reduce the positive rate of liver lipids. Golgi staining of brain tissue shows that the density of dendritic spines of neuronal cells in the ZSZ group has increased to a certain extent. Field potential results show that the excitatory postsynaptic potential(fEPSP) in the ZSZ group is significantly increased, and LTP is enhanced with significant differences(0-10 minutes, P<0.0001; 50-60 minutes, P<0.0001). Compared with the ZSZ group, the sham needle group has a certain reduction. There is no statistical difference in fEPSP enhancement, but there is a certain enhancement in LTP(0-10 minutes, P<0.01; 50-60 minutes, P<0.001). Conclusion: In AD mice, the intervention of ZSZ can be observed to affect the lipid metabolism levels of the mice. In the transcriptome of the hippocampus, which is the main functional area for learning and memory in mice, the Golgi staining and field potential, it can be seen that ZSZ affects the neurodegenerative disease pathways, increases the density of dendritic spines in mice, prolongs the maintenance time of LTP, enhances the excitability of synaptic nerves in mice, and improves the synaptic transmission efficiency.

关键词

Alzheimer's disease / zhisanzhen(ZSZ) / lipid metabolism / learning and memorizing / long-term potentiation(LTP)