Sahin, CerenAlbayrak, OzgurAkdeniz, Tuğba F.Akbulut, ZeynepYanıkkaya Demirel, GülderenArıcıoğlu, Feyze2024-07-122024-07-122016Sahin, C., Albayrak, O., Akdeniz, T.F., Akbulut, Z., Yanikkaya Demirel, G. and Aricioglu, F. (2016), Agmatine Reverses Sub-chronic Stress induced Nod-like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats. Basic Clin Pharmacol Toxicol, 119: 367-375.1742-7843https://hdl.handle.net/20.500.12415/3579The activation of Nod-like receptor protein 3 (NLRP3) has lately been implicated in stress and depression as an initiatormechanism required for the production of interleukin (IL)-1band IL-18. Agmatine, an endogenous polyamine widely distributedin mammalian brain, is a novel neurotransmitter/neuromodulator, with antistress, anxiolytic and antidepressant-like effects. In thisstudy, we examined the effect of exogenously administered agmatine on NLRP3 inflammasome pathway/cytokine responses inrats exposed to restraint stress for 7 days. The rats were divided into three groups: stress, stress+agmatine (40 mg/kg; i.p.) andcontrol groups. Agmatine significantly down-regulated the gene expressions of all stress-induced NLRP3 inflammasomecomponents (NLRP3, NF-jB, PYCARD, caspase-1, IL-1band IL-18) in the hippocampus and prefrontal cortex (PFC) andreduced pro-inflammatory cytokine levels not only in both brain regions, but also in serum. Stress-reduced levels of IL-4 andIL-10, two major anti-inflammatory cytokines, were restored back to normal by agmatine treatment in the PFC. The findings ofthe present study suggest that stress-activated NLRP3 inflammasome and cytokine responses are reversed by an acute administra-tion of agmatine. Whether antidepressant-like effect of agmatine can somehow, at least partially, be mediated by the inhibition ofNLRP3 inflammasome cascade and relevant inflammatory responses requires further studies in animal models of depression.eninfo:eu-repo/semantics/openAccessAgmatine ReversesSub-chronicStress inducedNod-like ReceptorArticle3754Q2367119