Esketamine relieves depressive-like behaviors in MPTP-induced Parkinson disease mice via GPR109A-dependent reduction of neuroinflammation
Brain Research Bulletin October 27, 2025 Shu Wang, Wei Song, Yuanyuan Gao et al.
A single dose of esketamine rapidly improved depressive-like behavior in a mouse model of Parkinson disease. The drug increased expression of GPR109A in the medial prefrontal cortex and reduced levels of pro-inflammatory markers TNF-α, IL-1β, and IL-6. Blocking GPR109A with mepenzolate bromide eliminated these benefits, indicating that GPR109A signaling is necessary for esketamine's antidepressant and anti-inflammatory effects. The findings suggest that esketamine alleviates Parkinson-related depression by suppressing microglial inflammation via GPR109A.