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: MDP, FK565 and LPS interacted with each other in modifying body temperature but not body weight (Fig. 3). Two-way ANOVA revealed a significant NOD × LPS interaction for the changes in body temperature (F(4,65) = 20.413, p < 0.001) (Fig. 3A). Post-hoc analysis showed that neither MDP (3 mg/kg), FK565 (0.003 mg/kg) nor the two doses of LPS induced changes of body temperature 4 h post-treatment. In contrast, combined treatment with MDP + LPS (0.83 mg/kg) and FK565 + LPS (0.83 mg/kg) evoked a strong hypothermic response compared to single treatment with the NOD agonists or LPS (Fig. 3A). Also the combination of MDP or FK565 with the lower dose of LPS (0.1 mg/kg) slightly decreased body temperature, the effect of MDP + LPS (0.1 mg/kg) reaching statistical significance when compared to MDP alone (Fig. 3A).
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.