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: 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: email@example.com.