Agmatine Reverses Sub-chronic Stress induced Nod-like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats

Sahin C., Albayrak O., Akdeniz T. F. , Akbulut Z., YANIKKAYA DEMİREL G., ARICIOĞLU F.

BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, vol.119, no.4, pp.367-375, 2016 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 119 Issue: 4
  • Publication Date: 2016
  • Doi Number: 10.1111/bcpt.12604
  • Page Numbers: pp.367-375


The activation of Nod-like receptor protein 3 (NLRP3) has lately been implicated in stress and depression as an initiator mechanism required for the production of interleukin (IL)-1 and IL-18. Agmatine, an endogenous polyamine widely distributed in mammalian brain, is a novel neurotransmitter/neuromodulator, with antistress, anxiolytic and antidepressant-like effects. In this study, we examined the effect of exogenously administered agmatine on NLRP3 inflammasome pathway/cytokine responses in rats exposed to restraint stress for 7 days. The rats were divided into three groups: stress, stress+agmatine (40 mg/kg; i.p.) and control groups. Agmatine significantly down-regulated the gene expressions of all stress-induced NLRP3 inflammasome components (NLRP3, NF-B, PYCARD, caspase-1, IL-1 and IL-18) in the hippocampus and prefrontal cortex (PFC) and reduced pro-inflammatory cytokine levels not only in both brain regions, but also in serum. Stress-reduced levels of IL-4 and IL-10, two major anti-inflammatory cytokines, were restored back to normal by agmatine treatment in the PFC. The findings of the present study suggest that stress-activated NLRP3 inflammasome and cytokine responses are reversed by an acute administration of agmatine. Whether antidepressant-like effect of agmatine can somehow, at least partially, be mediated by the inhibition of NLRP3 inflammasome cascade and relevant inflammatory responses requires further studies in animal models of depression.