Activation of sigma non-opioid intracellular receptor 1 (S1R) receptor inhibits plexin domain containing 2 (Plxdc2) driven microglial inflammation to ameliorate depressive-like behaviours in mice.
Analysis demonstrated that overexpressing Plxdc2 in mPFC microglia activated the JAK2-STAT1 pathway, enhanced NLG, shifting microglia towards a pro-inflammatory phenotype, worsening deficits in synaptic plasticity and induced depressive-like behaviour, which was reversible by the NLG inhibitor tunicamycin.