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    Agmatine reverses Sub-chronic stress induced Nod-like receptor Protein 3 (NLRP3) activation and cytokine response in rats
    (John Wiley & Sons, Ltd, 2016) Sahin, Ceren; Albayrak, Ozgur; Akdeniz, Tuğba F.; Akbulut, Zeynep; Yanıkkaya Demirel, Gülderen; Arıcıoğlu, Feyze
    The 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.