Limits...
Synergistic effects of NOD1 or NOD2 and TLR4 activation on mouse sickness behavior in relation to immune and brain activity markers.

Farzi A, Reichmann F, Meinitzer A, Mayerhofer R, Jain P, Hassan AM, Fröhlich EE, Wagner K, Painsipp E, Rinner B, Holzer P - Brain Behav. Immun. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria. Electronic address: aitak.farzi@medunigraz.at.

Show MeSH

Related in: MedlinePlus

Effects of MDP (3 mg/kg), FK565 (0.003 mg/kg) and LPS (doses as indicated) to reduce body temperature (A) and weight (B) in male mice. The graphs show the change in temperature 4 h post-treatment and body weight 21 h post-treatment. Body temperature and weight were measured before treatment and 4 and 26 h post-injection, respectively. The weight loss induced by the treatment is expressed as a percentage of the body weight measured pre-treatment. The values are means + SEM, n = 15 for VEH (merged from 2 separate experiments), n = 7–8 for other groups. Post-hoc analysis of significant NOD × LPS interactions in 2-way ANOVA: ##p < 0.01, MDP + LPS versus MDP or FK565 + LPS versus FK565. §§p < 0.01, MDP + LPS and FK565 + LPS versus LPS (0.83 mg/kg). Main factor effects without NOD × LPS interactions: ap < 0.01, LPS versus VEH. bp < 0.01, LPS 0.83 mg/kg versus LPS 0.1 mg/kg.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4295938&req=5

f0015: Effects of MDP (3 mg/kg), FK565 (0.003 mg/kg) and LPS (doses as indicated) to reduce body temperature (A) and weight (B) in male mice. The graphs show the change in temperature 4 h post-treatment and body weight 21 h post-treatment. Body temperature and weight were measured before treatment and 4 and 26 h post-injection, respectively. The weight loss induced by the treatment is expressed as a percentage of the body weight measured pre-treatment. The values are means + SEM, n = 15 for VEH (merged from 2 separate experiments), n = 7–8 for other groups. Post-hoc analysis of significant NOD × LPS interactions in 2-way ANOVA: ##p < 0.01, MDP + LPS versus MDP or FK565 + LPS versus FK565. §§p < 0.01, MDP + LPS and FK565 + LPS versus LPS (0.83 mg/kg). Main factor effects without NOD × LPS interactions: ap < 0.01, LPS versus VEH. bp < 0.01, LPS 0.83 mg/kg versus LPS 0.1 mg/kg.

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).


Synergistic effects of NOD1 or NOD2 and TLR4 activation on mouse sickness behavior in relation to immune and brain activity markers.

Farzi A, Reichmann F, Meinitzer A, Mayerhofer R, Jain P, Hassan AM, Fröhlich EE, Wagner K, Painsipp E, Rinner B, Holzer P - Brain Behav. Immun. (2014)

Effects of MDP (3 mg/kg), FK565 (0.003 mg/kg) and LPS (doses as indicated) to reduce body temperature (A) and weight (B) in male mice. The graphs show the change in temperature 4 h post-treatment and body weight 21 h post-treatment. Body temperature and weight were measured before treatment and 4 and 26 h post-injection, respectively. The weight loss induced by the treatment is expressed as a percentage of the body weight measured pre-treatment. The values are means + SEM, n = 15 for VEH (merged from 2 separate experiments), n = 7–8 for other groups. Post-hoc analysis of significant NOD × LPS interactions in 2-way ANOVA: ##p < 0.01, MDP + LPS versus MDP or FK565 + LPS versus FK565. §§p < 0.01, MDP + LPS and FK565 + LPS versus LPS (0.83 mg/kg). Main factor effects without NOD × LPS interactions: ap < 0.01, LPS versus VEH. bp < 0.01, LPS 0.83 mg/kg versus LPS 0.1 mg/kg.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4295938&req=5

f0015: Effects of MDP (3 mg/kg), FK565 (0.003 mg/kg) and LPS (doses as indicated) to reduce body temperature (A) and weight (B) in male mice. The graphs show the change in temperature 4 h post-treatment and body weight 21 h post-treatment. Body temperature and weight were measured before treatment and 4 and 26 h post-injection, respectively. The weight loss induced by the treatment is expressed as a percentage of the body weight measured pre-treatment. The values are means + SEM, n = 15 for VEH (merged from 2 separate experiments), n = 7–8 for other groups. Post-hoc analysis of significant NOD × LPS interactions in 2-way ANOVA: ##p < 0.01, MDP + LPS versus MDP or FK565 + LPS versus FK565. §§p < 0.01, MDP + LPS and FK565 + LPS versus LPS (0.83 mg/kg). Main factor effects without NOD × LPS interactions: ap < 0.01, LPS versus VEH. bp < 0.01, LPS 0.83 mg/kg versus LPS 0.1 mg/kg.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria. Electronic address: aitak.farzi@medunigraz.at.

Show MeSH
Related in: MedlinePlus