Effect of Du Meridian pushing on synaptic pruning function of microglia mediated by C1q/C3 in hippocampus of adolescent mice with autism spectrum disorder
10.3969/j.issn.1000-4718.2025.10.012
- VernacularTitle:督脉推法对孤独症谱系障碍模型小鼠青少年期海马内C1q/C3介导小胶质细胞突触修剪功能的影响
- Author:
Yinan CHEN
1
;
Shatong ZHAO
;
Mingan HU
;
Mengjuan MA
;
Wu LI
;
Xiang FENG
;
Jiangshan LI
;
Yuxing ZHANG
Author Information
1. 湖南中医药大学针灸推拿与康复学院,湖南 长沙 410208
- Publication Type:Journal Article
- Keywords:
direct stimulation of the Du Meridion;
autism spectrum disorder;
microglia;
synaptic pruning;
complement
- From:
Chinese Journal of Pathophysiology
2025;41(10):1972-1982
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate whether direct stimulation of the Du Meridian improves autism-like behaviors in mice by modulating synaptic pruning.METHODS:Pregnant mice received intraperitoneal injections of valproic acid(VPA)or saline on gestational day 12.5.Offspring from saline-treated mice were assigned to the saline group.Offspring from VPA-treated mice were randomly divided into the model(VPA)group and the VPA-model-DuMaiTuiFa(VPA-DMTF)group.Each group included five mice.The VPA-DMTF group received direct stimulation along the Du Mai at 80 times per minute,10 minutes per session,twice daily for 21 days.After treatment,behavioral tests were conducted,in-cluding the three-chamber test for social interaction and the open field test for anxiety-like behavior.Hippocampal tissue was collected for analysis.Golgi staining was used to assess dendritic spine density.Immunofluorescence staining for post-synaptic denisty protein(PSD95)and synapsin 1(SYN1)was performed to evaluate synaptic protein expression.Staining for ionized calcium-binding adapter molecule 1(IBA1)and CD68 was used to assess microglial phagocytosis.Western blot analysis was conducted to evaluate hippocampal expression levels of PSD95,SYN1,IBA1,complement component 1,q subcomponent(C1q),complement component 3(C3),and complement receptor 3(CR3).RESULTS:Compared with the saline group,VPA mice showed reduced social behavior and increased anxiety(P<0.05).The expression levels of IBA1,PSD95,and SYN1 were significantly increased(P<0.05),whereas C1q,C3,and CR3 were significantly de-creased(P<0.05).Microglial phagocytosis declined.Immunofluorescence analysis showed increased levels of synaptic proteins(PSD95 and SYN1)in the VPA group(P<0.05).Golgi staining revealed a higher dendritic spine density and an increased proportion of immature dendritic spines(P<0.05).Compared with the VPA group,VPA-DMTF mice showed improved behavior,reduced IBA1,PSD95,and SYN1 levels(P<0.05),and increased expression of C1q,C3,and CR3(P<0.05).Microglial phagocytosis was enhanced,and dendritic spine number was reduced.CONCLUSION:Direct stimulation of the Du Mai alleviates autism-like behaviors in mice.This effect may be mediated by upregulation of comple-ment proteins C1q and C3,which enhance microglia-mediated synaptic pruning and reduce synaptic overabundance.
