Synergistic effects of NOD1 or NOD2 and TLR4 activation on mouse sickness behavior in relation to immune and brain activity markers.
Bottom Line: When given alone, FK565 and MDP had only minor effects.Immunohistochemical visualization of c-Fos in the brain revealed that NOD2 synergism with TLR4 resulted in increased activation of cerebral nuclei relevant to sickness.Our findings demonstrate that the known interactions of NLRs and TLRs at the immune cell level extend to interactions affecting brain function and behavior.
Affiliation: Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria. Electronic address: email@example.com.Show MeSH
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Mentions: The expression of cytokine mRNAs in the brain was measured 3 and 26 h after injection of the PRR agonists in order to analyze cytokine expression at the time of predominant sickness and depression-like behavior, respectively (Fig. 6). When cytokine mRNA was assessed 3 h post-treatment, two-way ANOVA revealed a NOD × LPS interaction for the expression of IFN-γ mRNA (F(2,42) = 5.911, p < 0.01) and a trend for IL-6 mRNA expression (F(2,42) = 2.774, p = 0.07). Post-hoc analysis disclosed that while neither MDP (3 mg/kg), FK565 (0.003 mg/kg) nor LPS (0.1 mg/kg) alone increased mRNA expression of IFN-γ or IL-6, combined treatment with MDP + LPS or FK565 + LPS increased IFN-γ and IL-6 mRNA expression compared to LPS or MDP and FK565, respectively (Fig. 6A and C). In contrast, expression of IL-1β mRNA depended on LPS (F(1,42) = 24.984, p < 0.001) and the NOD agonists (F(2,42) = 3.174, p ⩽ 0.05) without a significant interaction (Fig. 6B). Likewise, TNF-α mRNA expression depended on LPS (F(1,42) = 25.735, p < 0.001) and the NOD agonists (F(2,42) = 8.535, p < 0.001) without a significant interaction (Fig. 6D).
Affiliation: Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria. Electronic address: firstname.lastname@example.org.