Mechanism of electroacupuncture on microglial and cortical neurons in mice with amyotrophic lateral sclerosis model
10.3969/j.issn.1001-1242.2025.02.002
- VernacularTitle:电针对肌萎缩侧索硬化症模型小鼠皮质小胶质细胞/神经元活性影响的机制研究
- Author:
Weijia ZHAO
1
;
Jiawei ZENG
;
Junyang LIU
Author Information
1. 陕西中医药大学第二临床医学院,陕西省咸阳市,712046
- Publication Type:Journal Article
- Keywords:
amyotrophic lateral sclerosis;
electroacupuncture intervention;
microglia;
neuroinflammation;
cere-bral cortex
- From:
Chinese Journal of Rehabilitation Medicine
2025;40(2):171-179
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the effect of electroacupuncture(EA)on microglia and cortical excitability in hSOD1G93A mice and to explore the potential central mechanisms of EA intervention to improve motor func-tion in amyotrophic lateral sclerosis(ALS)mice.Method:The present study includes 2 parts.① Sixteen hSOD1G93A mice were randomly divided into model group and EA group(n=8 per group).Eight hSOD1G93A-negative mice were used as the blank group.The EA group was applied to the Baihui,bilateral Tianzhu and bilateral Tianshu acupoints(10 minutes/session,5 sessions/week,for 3 weeks).After 3 weeks of EA,hind limb functional neurologic score and open field test were used to evaluate the changes in motor function of mice.The concentrations of IL-1β and IL-6 were de-tected by ELISA.Immunofluorescence staining and flow cytometry were employed to observe the rate of Iba-1 positive cells and cell phenotypes in the cerebral cortex.②Twenty-one hSOD1G93A mice and seven wild-type mice were included.The Chemical genetic excitatory virus[rAAV-CaMKIIa-hM3D(Gq)-EGFP-WPRE-hGH poly A]was injected into the primary motor cortex(M1)area of the mice.After 21 days,four mice(3 SOD1G93A and 1 wild-type)were randomly selected for fluorescent microscopy to confirm viral expression.The remaining hSOD1G93A mice were randomly divided into 3 groups:model,EA group,and chemogenetic excitatory virus(intraperitoneal injection of clozapine-N-oxide[CNO])combined with EA group,with 6 mice per group.The rate of c-Fos positive cells in the cerebral cortex was observed by immunofluorescence.The open field experiment was used to evaluate the changes in motor function of mice.Result:Compared with the blank group,the model group showed significantly reduced total distance in the open-field test and increased neurologic scores(P<0.01),elevated serum IL-1β and IL-6 levels,increased corti-cal Iba-1 and c-Fos expression(P<0.01),and higher proportions of M1 and M2 microglia(P<0.01,P<0.05).Compared with the model group,the total distance of open field movement was prolonged and the neurologi-cal score decreased in the EA group(P<0.01,P<0.05).The contents of serum IL-1β and IL-6,the expression of Iba-1、c-Fos in cerebral cortex were decreased in the EA group(P<0.01,P<0.05),with an increased propor-tion of M2 microglia(P<0.05);the rate of c-Fos positive cells decreased in the virus+EA group,and the total distance of open field movement was prolonged.Conclusion:EA intervention can improve motor function in ALS mice.The underlying mechanism may be re-lated to suppress the activity of microglia,reduce the expression of inflammatory cytokines and further to de-crease the excitability of M1 cortical neurons.