Acupuncture improves perimenopausal depression via a mechanism involving activation of the phosphatidylinositol 3-kinase/serine-threonine protein kinase/mechanistic target of rapamycin pathway in a rat model.

Background: Perimenopausal depression (PMD), a psychiatric disorder triggered by declining ovarian function before menopause, remains poorly understood in terms of therapeutic mechanisms. While acupuncture has demonstrated efficacy in alleviating PMD symptoms, its molecular basis requires further exploration. This study aimed to investigate whether acupuncture ameliorates PMD by modulating phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (AKT)/mammalian target of rapamycin (mTOR) signaling in a rat model.

Methods: The female SD rats were randomly assigned to four groups: model, blank, acupuncture, and Western medicine, with each group consisting of six rats. The acupuncture group received acupuncture at the Baihui (GU20), Shenshu (BL23), Ganshu (BL18), and Sanyinjiao points for 28 consecutive sessions over 4 weeks. A PMD rat model was established through ovariectomy (OVX) combined with chronic unpredictable mild stress. Depression-related behaviors were measured through the forced swimming test, sucrose preference test, and open field test. The levels of estrogen (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and gonadotropin-releasing hormone (GnRH) in serum were determined through ELISA. The expression of PI3K, AKT, and mTOR in the hippocampal Cornu Ammonis 1 (CA1) region was analyzed by reverse transcription quantitative PCR and Western blotting.

Results: Acupuncture markedly attenuated depression-like behaviors and hippocampal pathology in PMD rats. It restored hormonal balance by elevating serum E2 while suppressing FSH, LH, and GnRH. At the molecular scale, acupuncture enhanced the expression of both mRNA and proteins of PI3K, AKT, and mTOR in the hippocampus CA1 region.

Conclusion: Acupuncture alleviates PMD through dual regulation of sex hormone homeostasis and activation of the PI3K/AKT/mTOR pathway, suggesting a potential mechanism for its antidepressant effects in perimenopause.