Synergistic effects of NOD1 or NOD2 and TLR4 activation on mouse sickness behavior in relation to immune and brain activity markers.
Bottom Line: Intraperitoneal injection of FK565 (0.001 or 0.003mg/kg) or MDP (1 or 3mg/kg) 4h before LPS (0.1 or 0.83mg/kg) significantly aggravated and prolonged the LPS-evoked sickness behavior as deduced from a decrease in locomotion, exploration, food intake and temperature.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.
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.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: email@example.com.