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Antidepressant-Like Effects of Electroacupuncture by Regulating NLRP3-mediated Hippocampal Inflammation and
Wa Cai1, Xi-Fang Wei2, Larissa Tao1
1Department of Acupuncture, Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Objective:
This study aimed to investigate whether the antidepressant-like effects of electroacupuncture (EA) are associated with the regulation of inflammation and pyroptosis mediated by the NLRP3 inflammasome, as well as the protection of neuron cells in the hippocampus (HP) in a rat model of post-stroke depression (PSD).
Methods:
Depressive-like behaviors (DLBs) in PSD rats were evaluated through a series of behavioral tests. The expression levels of NLRP3, caspase-1 (Casp-1), and apoptosis-associated speck-like protein (ASC), as well as the cleavage product gasdermin D (GSDMD), were assessed using real-time PCR (RT-PCR), immunofluorescence, and Western blot (WB). IL-1β and IL-18 levels were measured by RT-PCR and WB. To upregulate NLRP3 expression, adeno-associated virus (AAV) was injected into the hippocampus. Nissl staining was employed to evaluate neuronal morphology and count in the hippocampus.
Results:
EA significantly alleviated DLBs in PSD rats and suppressed the overexpression of NLRP3, Casp-1, ASC, GSDMD, IL-1β, and IL-18 in the ischemic hippocampus. NLRP3 overexpression attenuated the therapeutic effects of EA on both behavioral outcomes and neuroinflammatory markers.
Conclusions:
EA mitigated hippocampal inflammation and pyroptosis in PSD by downregulating NLRP3 inflammasome activation, indicating that NLRP3 may serve as a potential therapeutic target for PSD.
