Effect of electroacupuncture at "Hegu" (LI4) and "Taichong" (LR3) on DNA methylation of the SLC6A4 gene promoter in the hippocampus of depressed rats.
10.13703/j.0255-2930.20240902-k0005
- Author:
Xi ZHANG
1
;
Shengyong SU
2
;
Xin LI
3
;
Tian WANG
3
Author Information
1. Graduate School, Guangxi University of CM, Nanning 530001, China; Department of Acupuncture and Moxibustion, First Affiliated Hospital of Guangxi University of CM, Nanning 530023; Guangxi Key Laboratory of Molecular Medicine in Prevention and Treatment of Major Diseases with TCM, Nanning
2. Department of Acupuncture and Moxibustion, First Affiliated Hospital of Guangxi University of CM, Nanning 530023; Guangxi Key Laboratory of Molecular Medicine in Prevention and Treatment of Major Diseases with TCM, Nanning
3. Graduate School, Guangxi University of CM, Nanning 530001, China.
- Publication Type:Journal Article
- Keywords:
SLC6A4 gene promoter DNA methylation;
depression;
electroacupuncture (EA);
hippocampus
- MeSH:
Animals;
Electroacupuncture;
Male;
Hippocampus/metabolism*;
Rats, Sprague-Dawley;
Rats;
Acupuncture Points;
DNA Methylation;
Depression/metabolism*;
Promoter Regions, Genetic;
Serotonin Plasma Membrane Transport Proteins/metabolism*;
Humans
- From:
Chinese Acupuncture & Moxibustion
2025;45(11):1609-1616
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To observe the effect of electroacupuncture (EA) at "Hegu" (LI4) and "Taichong" (LR3) on DNA methylation of the solute carrier family 6 member 4 (SLC6A4) gene promoter region in the hippocampus of depressed rats, and to explore the potential antidepressant mechanism of EA.
METHODS:Thirty male Sprague-Dawley rats were randomly divided into a blank group, a model group, a medication group, a 5-Azacytidine (5-AZA) group, and an EA group, 6 rats in each group. Depression models were established in the model group, the medication group, the 5-AZA group, and the EA group using chronic unpredictable mild stress (CUMS) combined with solitary housing. The medication group was treated with intragastric administration of fluoxetine hydrochloride capsules; the 5-AZA group was treated with intraperitoneal injection of 5-AZA; the EA group was treated with EA at bilateral "Hegu" (LI4) and "Taichong" (LR3), with disperse-dense wave, frequency of 2 Hz/100 Hz, and intensity of 1-1.2 mA, 20 min each session. All the treatment was given in three groups once daily for 21 consecutive days. Behavioral changes were evaluated by sucrose preference test, open field test, and novelty-suppressed feeding test. Serum levels of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) were measured by ELISA. The expression of SLC6A4 and 5-HT1AR protein and mRNA in hippocampus was detected by Western blot and real-time quantitative PCR, respectively. DNA methylation status of the SLC6A4 promoter region in hippocampal tissue was analyzed by bisulfite sequencing PCR (BSP).
RESULTS:Compared with the blank group, the model group showed decreased sucrose preference, reduced total locomotor distance, and prolonged latency to feeding (P<0.05), decreased serum 5-HT, DA, and NE levels (P<0.05), downregulated hippocampal SLC6A4 and 5-HT1AR protein and mRNA expression (P<0.05), and increased CpG site methylation rate of the SLC6A4 promoter region (P<0.05). Compared with the model group, the medication group, the 5-AZA group, and the EA group exhibited increased sucrose preference, increased total locomotor distance, shortened latency to feeding (P<0.05), elevated serum 5-HT, DA, and NE levels (P<0.05), upregulated hippocampal SLC6A4 and 5-HT1AR protein and mRNA expression (P<0.05), and reduced CpG site methylation rate of the SLC6A4 promoter (P<0.05). Compared with the medication group and the 5-AZA group, the EA group showed higher sucrose preference, greater total locomotor distance, shorter latency to feeding (P<0.05), and increased serum DA and NE levels (P<0.05).
CONCLUSION:EA could improve depressive behaviors in depressed rat models. The underlying mechanism may involve inhibition of SLC6A4 hypermethylation in the hippocampus on the serotonergic system, upregulation of SLC6A4 and 5-HT1AR protein and mRNA expression, and elevation of monoamine neurotransmitters such as 5-HT.
