Work

Electroacupuncture prevents depression via PINK1/Parkin-driven suppression of NLRP3 activation

Year: 2025

Type: article

Abstract: Although several hypotheses have been proposed to elucidate the etiology of depression, its pathogenesis and effective treatment remain elusive. electroacupuncture (EA), a non-pharmacological therapy, exerts antidepressant effects through promoting the inhibition of immune pathways activation and the release of cytokines. Still, the underlying mechanisms of EA have yet to be fully explored. When it comes to the pathogenesis of depression, various previous studies have demonstrated that neuroinflammation and mitochondrial autophagy hold critical roles. The current study found that EA greatly attenuated the generation of inflammatory factors caused by chronic restraint stress (CRS), such as IL-1β, IL-6, and TNF-α. Notably, EA diminished the levels of the Nod-like receptor (NLR) protein family, pyrin domain containing three (NLRP3) inflammasome and pyroptosis-related proteins, which includes NLRP3, apoptosis-associated speck protein‌ (ASC), and active caspase-1. Further studies showed that an association could be made between this anti-inflammatory effect of EA and the regulation of mitochondrial autophagy. Actually, EA can promote autophagy via the PINK1/Parkin mitochondrial autophagy pathway to enhance the clearance of damaged mitochondria and attenuate NLRP3 inflammasome activation. Our data suggest that EA ameliorates depressive behavior in CRS model rats and inhibits NLRP3 inflammasome activation by promoting mitochondrial autophagy, thereby exerting neuroprotective and antidepressant effects. • Electroacupuncture Mitigates Depressive Behavior: Electroacupuncture (EA) exerts significant antidepressant effects in a chronic restraint stress (CRS) model, evidenced by the amelioration of depressive-like behaviors in rats. • Modulation of Inflammatory Cytokines: EA effectively reduces the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), highlighting its role in modulating neuroinflammation associated with depression. • Inhibition of NLRP3 Inflammasome Activation: EA attenuates the activation of the NLRP3 inflammasome and associated pyroptotic proteins (ASC, caspase-1), underscoring its potential in regulating innate immune responses in the brain. • Enhancement of Mitochondrial Autophagy via PINK1/Parkin Pathway: EA promotes mitochondrial quality control by activating the PINK1/Parkin pathway, facilitating the clearance of damaged mitochondria and reducing inflammasome activation, which may contribute to its neuroprotective effects.

Source: Brain Research Bulletin

DOI: 10.1016/j.brainresbull.2025.111609