Esketamine alleviates LPS-induced depression-like behavior by activating Nrf2-mediated anti-inflammatory response in adolescent mice.
Neuroscience February 16, 2025 Xinxu Ma, Shanshan Xue, Hongzhe Ma et al. 12 citations
A single dose of esketamine alleviates depressive-like behaviors in adolescent male mice exposed to the inflammatory agent LPS. The antidepressant effect is linked to increased expression of the Nrf2 protein and reduced levels of inflammatory cytokines (TNF-α, IL-1β, iNOS) in the brain's prefrontal cortex and hippocampus. Blocking Nrf2 with the inhibitor ML385 reversed both the behavioral and anti-inflammatory effects of esketamine. In the blood, esketamine also reduced pro-inflammatory and increased anti-inflammatory cytokines, an effect again blocked by Nrf2 inhibition. The findings suggest esketamine's rapid antidepressant action may work through activating Nrf2-mediated anti-inflammatory signaling.