To investigate the effect of electroacupuncture (EA) on the behaviors of lipopolysaccharide (LPS)-induced depression-like mice and explore the potential molecular mechanism of the antidepressant effect of EA using transcriptomics sequencing technology.

Thirty-six male specific pathogen-free-grade C57BL/6J mice were divided into the normal, the model, and the EA groups using the random number table method, with 12 mice per group. The EA group received a daily 20-minute EA at the "Baihui" and "Yintang" acupoints for 7 days. After 7 days of EA treatment, 1.5 mg/kg LPS was injected intraperitoneally into the model and EA groups, whereas the normal group received an injection of an equal volume of saline solution. Depressive behaviors were assessed using the open-field test, tail-suspension test, and other relevant tests. Pathologic morphology of the hippocampus tissue was determined using hematoxylin-eosin staining. Transcriptomics technology was used to identify differentially expressed genes in the hippocampus, and bioinformatics analysis was performed. Real-time fluorescence quantitative PCR was performed to detect the mRNA expressions of hematopoietic cell kinase (Hck), adhesion G protein-coupled receptor E1 (Adgre1), Toll-like receptor 2 (Tlr2), and Gm49037 in the hippocampus.

Compared to the normal group, mice in the model group exhibited a decrease in total travel distance, central travel distance, center area time (P < 0.01), as well as an increase in tail-suspension immobility time (P < 0.05). Hippocampal neurons were loosely arranged, and some neurons had blurred boundaries. Compared to the model group, mice in the EA group showed an increase in open-field total travel distance, central travel distance, center area time (P < 0.05), as well as a decrease in tail-suspension immobility time (P < 0.01); Additionally, hippocampal neurons were more tightly arranged, exhibiting clearer morphology and structure. Transcriptomic analysis revealed that 779 differentially expressed genes were identified in the model group compared to the normal group, whereas 172 genes differed between the EA and model groups. Nineteen genes were upregulated in the model group but downregulated in the EA group, and ten genes were down-regulated in the model group but up-regulated in the EA group. Gene Ontology Functional Analysis indicated that these genes primarily function in immune responses, Toll-like receptor activity, cell surface receptor signaling pathways, and interleukin - 10 production. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed enrichment in inflammation-related pathways, including Toll-like receptor signaling pathway and tumor necrosis factor signaling pathway. Compared to the normal group, Hck, Adgre1, and Tlr2 mRNA expressions were elevated in the model group (P < 0.01), whereas there was a decrease tendency for Gm49037 mRNA expression and there was no significant difference (P > 0.05); compared to the model group, Hck, Adgre1, and Tlr2 mRNA expressions were decreased in the EA group (P < 0.05), whereas there was an increase tendency for Gm49037 mRNA expression and there was no significant difference (P > 0.05).

EA alleviated depressive-like behavior and pathological damage in the hippocampus in LPS-induced mice, which may be related to attenuating hippocampal inflammatory pathways, and Hck, Adgre1, and Tlr2 genes may be the potential targets for its effect.

To observe the effect of manual acupuncture stimulation on changes of behavior and hippocampal signaling pathways of AMP-activated kinase (AMPK)/UNC-51-like kinase 1 (ULK1) in rats with chronic unpredictable mild stress (CUMS)-induced depression, so as to explore its molecular mechanism underlying improvement of depression.

Thirty-two male SD rats were randomly divided into normal control, model, acupuncture and medication (fluoxetine) groups, with 8 rats in each group. The depression model was established by using CUMS (fasting, water depredation, restraint, swimming in cold water, crowding, stroboscope stimulation, and tail clipping, each of which was used once a week) for 6 weeks. Manual acupuncture stimulation was applied to “Baihui” (GV20) and “Yintang” (EX-HN3) for 10 min, once daily, 6 times a week for 6 weeks before every-day modeling. Rats of the medication group received gavage of fluoxetine (10 mg/kg) once a day for 6 weeks before every-day modeling. The percentage of sucrose preference, and the percentages of open arm times and open arm time in the elevated plus maze experiments were detected. The expression levels of AMPK, phosphorylated (p)-AMPK, ULK1, p-ULK1, mammalian target of rapamycin (mTOR) and p-mTOR proteins in the hippocampus tissue were detected by Western blot, and the expression of autophagy effecting protein (Beclin-1) and the selective autophagy receptors (p62) mRNA in the hippocampal tissue was detected using real-time fluorescence quantitative PCR, respectively.

Compared with the normal group, the percentage of sucrose preference, percentage of times of entering the open arm and percentage of open arm time, the expression levels of p-AMPK/AMPK ratio, p-ULK1/ULK1 ratio of proteins, and Beclin-1 mRNA were significantly decreased (P<0.01, P<0.05), and the expression levels of p-mTOR/mTOR ratio and p62 mRNA were significantly increased (P<0.01, P<0.05) in the model group. In comparison with the model group, the percentage of sucrose preference, percentage of open arm times and open arm time, the expression levels of p-AMPK/AMPK ratio, p-ULK1/ULK1 ratio of proteins, and Beclin-1 mRNA were significantly increased in both acupuncture and medication groups (P<0.01, P<0.05), while the expression levels of p-mTOR/mTOR ratio of proteins, and p62 mRNA were markedly decreased only in the medication group (P<0.05).

Acupuncture treatment can alleviate depression-like behavior in CUMS rats, which may be related to its functions in up-regulating AMPK/ULK1 signaling pathway to induce cellular autophagy in the hippocampus.