Acupuncture as a modulator of microglial polarization and pyroptosis in depression: evidence from a chronic unpredictable mild stress rat model.

Abstract

BACKGROUND: Depression is a common psychiatric disorder, with stress-induced neuroinflammation playing a crucial role in its pathogenesis. Acupuncture has been demonstrated to be both effective and safe in the treatment of depression, but its precise mechanisms remain unclear. METHOD: This study investigated acupuncture's effects on neuroglia-associated neuroinflammation in chronic unpredictable mild stress (CUMS)-induced depressive rats. Rats underwent CUMS for 28 days, with the acupuncture group receiving treatment at Shangxing (GV23) and Fengfu (GV16) every other day. The fluoxetine group received daily intragastric fluoxetine. Depression-like behaviors were assessed through body weight measurements and behavioral tests. Hippocampal pathology was examined using hematoxylin and eosin (H&E) staining, and immunofluorescence was used to detect activated microglia in the hippocampus. Western blotting (WB) analyzed key proteins associated with microglial phenotypes, including CD16, inducible nitric oxide synthase (iNOS), CD206, and arginase-1 (Arg-1). Additionally, nuclear factor kappa B (NF-κB), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cysteine-aspartic acid protease-1 (caspase-1), and gasdermin D (GSDMD) levels were measured using WB and reverse transcription-polymerase chain reaction (RT-PCR). Cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and interleukin-4 (IL-4) were quantified via enzyme-linked immunosorbent assay (ELISA). RESULT: Acupuncture significantly alleviated CUMS-induced depression-like behaviors, enhancing sucrose preference and reducing immobility time. It inhibited microglial M1 polarization, downregulated NF-κB and NLRP3 expression, and suppressed pyroptosis-related proteins like caspase-1 and GSDMD. CONCLUSION: Acupuncture alleviates depression-like behaviors in CUMS-induced rats by modulating microglial polarization and inhibiting neuroinflammation-mediated pyroptosis. Our findings provide further evidence supporting acupuncture as a viable strategy for depression treatment.