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- Title
Agmatine Reverses Sub-chronic Stress induced Nod-like Receptor Protein 3 ( NLRP3) Activation and Cytokine Response in Rats.
- Authors
Sahin, Ceren; Albayrak, Ozgur; Akdeniz, Tuğba F.; Akbulut, Zeynep; Yanikkaya Demirel, Gulderen; Aricioglu, Feyza
- Abstract
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)-1β 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-κB, PYCARD, caspase-1, IL-1β 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.
- Subjects
AGMATINE; NEUROTRANSMITTER receptors; ANTIDEPRESSANTS; ANIMAL models of inflammation; CYTOKINES; DISEASES; PSYCHOLOGICAL stress
- Publication
Basic & Clinical Pharmacology & Toxicology, 2016, Vol 119, Issue 4, p367
- ISSN
1742-7835
- Publication type
Article
- DOI
10.1111/bcpt.12604