Electroacupuncture ameliorates chronic unpredictable mild stress-induced depression-like behavior and cognitive impairment through suppressing oxidative stress and neuroinflammation in rats.

BACKGROUND: Depression is associated with lowered mood, anxiety, anhedonia, cognitive impairments, and even suicidal tendencies in severe cases. Yet few studies have directed acupuncture's mechanism toward enhancing axonal repair correlated with synaptic plasticity and anti-inflammatory effects related to oxidative stress in the hippocampus. METHODS: Male Sprague-Dawley (SD) rats were randomly divided into control group (CON), chronic unpredictable mild stress (CUMS) group, CUMS + electroacupuncture group (EA), and CUMS + fluoxetine group (FLX) (n = 10/group). Rats were given a 28-day treatment at the Shangxing (GV23) and Fengfu (GV16) acupoints with electroacupuncture or fluoxetine (2.1 mg/kg). RESULTS: Rats exposed to CUMS induced depression-like behaviors and spatial learning-memory impairment, changed the ionized calcium binding adaptor molecule 1 (IBA-1), Vglut1, myelin basic protein (MBP), and postsynaptic density protein 95 (PSD95) level of hippocampal, increased the Nod-like receptor protein 3 (NLRP3), atypical squamous cell (ASC), Caspase level and hippocampal reactive oxygen species (ROS), and prompted the activation of Epha4-mediated signaling and an inflammatory response. Conversely, electroacupuncture administration reduced these changes and prevented depression-like behaviors and cognitive impairment. Electroacupuncture also promoted hippocampal expression of Sirtuin1(SIRT1), Nuclear factor erythroid 2-like (Nrf2), Heme oxygenase-1 (HO-1); reduced the expression of interleukin-1ß (IL-1ß), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-α); and prevented neural damage, particularly the synaptic myelin sheath, and neuroinflammation by regulating Eph receptor A4 (EphA4) in the hippocampal. CONCLUSION: These results indicate that electroacupuncture prevents depression-like behaviors with cognitive impairment and synaptic and neuronal damage, probably by reducing EphA4, which mediates ROS hyperfunction and the inflammatory response.

Anti-depressant effects of acupuncture: The insights from NLRP3 mediated pyroptosis and inflammation.

The NLRP3-mediated pyroptosis, which could affect inflammation response, plays a key role in the development of depression. Acupuncture has been shown to be an effective treatment for depression. In this study, we aimed to determine whether acupuncture could confer antidepressant activity via decreasing NLRP3-mediated pyroptosis by reducing inflammation. Here, depression model of rats was induced by chronic unpredictable mild stress (CUMS) for 4 weeks. Acupuncture group was subjected to acupuncture at the Shangxing (GV23) and Fengfu (GV16) acupoints for 20 min every other day (a total of 14 times). Fluoxetine group was administered with fluoxetine (2.1 mg/kg with the concentration of 0.21 mg/mL) by oral gavage (1 mL/100 g) once a day for 28 days. Rats' depression-like phenotypes were reflected with behavioral tests and biological detection methods. Results showed that acupuncture significantly improved the depression-like behavior of CUMS rat, suppressed the expressions of NLRP3, ASC, caspase-1, GSDMD, IL-1ß, IL-18, HMGB1, IFN-γ, IL-6 and TNF-α in the serum and hippocampus, restored the %area of microglia, astrocytes and neuronal cells in the hippocampus. These indicate that acupuncture can prevent CUMS-induced depression-like behaviors by reducing NLRP3-mediated pyroptosis and inflammation.