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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.

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Effects of MDP (3 mg/kg), FK565 (0.003 mg/kg) and LPS (doses as indicated) on behavior in the OF 21 h post-treatment in male mice. The graphs show the time spent in the central area (A + D), the number of entries into the central area (B + E) and the total distance traveled (C + F) during the 5 min test session. The values are means + SEM, n = 7–8. (A–C): Post-hoc analysis of significant NOD × LPS interactions in 2-way ANOVA: ∗p < 0.05, versus VEH. ##p < 0.01, MDP + LPS versus MDP or FK565 + LPS versus FK565. §§p < 0.01, MDP + LPS or FK565 + LPS versus LPS. Main factor effects without NOD × LPS interactions: ap < 0.01, LPS versus VEH. (D–F): One-way ANOVA: ∗p < 0.05, ∗∗p < 0.01, versus VEH.
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f0020: Effects of MDP (3 mg/kg), FK565 (0.003 mg/kg) and LPS (doses as indicated) on behavior in the OF 21 h post-treatment in male mice. The graphs show the time spent in the central area (A + D), the number of entries into the central area (B + E) and the total distance traveled (C + F) during the 5 min test session. The values are means + SEM, n = 7–8. (A–C): Post-hoc analysis of significant NOD × LPS interactions in 2-way ANOVA: ∗p < 0.05, versus VEH. ##p < 0.01, MDP + LPS versus MDP or FK565 + LPS versus FK565. §§p < 0.01, MDP + LPS or FK565 + LPS versus LPS. Main factor effects without NOD × LPS interactions: ap < 0.01, LPS versus VEH. (D–F): One-way ANOVA: ∗p < 0.05, ∗∗p < 0.01, versus VEH.

Mentions: The behavior in the OF was modified by MDP, FK565 and LPS in a compound-, combination- and time-dependent manner (Fig. 4). The OF test was used to assess anxiety-like behavior as deduced from the time spent in the central area and the entries made to the central area of the OF and locomotion as deduced from the traveling distance (Fig. 4). In experiments with the higher dose of LPS (0.83 mg/kg), two-way ANOVA revealed a significant NOD × LPS interaction for the changes in locomotion (F(2,42) = 3.168, p ⩽ 0.05). Post-hoc analysis showed that while the NOD agonists did not impact on locomotion, treatment with LPS (0.83 mg/kg) slightly decreased the traveling distance in the OF (Fig. 4C). Furthermore, combined treatment with MDP (3 mg/kg) + LPS (0.83 mg/kg) or FK565 (0.003 mg/kg) + LPS (0.83 mg/kg) further diminished the distance traveled when compared with LPS alone, or MDP and FK565, respectively (Fig. 4C). The entries made into the center of the field depended on LPS (F(1,42) = 31.001, p < 0.001), while the effect of the NOD agonists and their interaction with LPS did not reach significance (Fig. 4B). The time spent in the central area of the OF was not significantly affected by any of the compounds (Fig. 4A).


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) on behavior in the OF 21 h post-treatment in male mice. The graphs show the time spent in the central area (A + D), the number of entries into the central area (B + E) and the total distance traveled (C + F) during the 5 min test session. The values are means + SEM, n = 7–8. (A–C): Post-hoc analysis of significant NOD × LPS interactions in 2-way ANOVA: ∗p < 0.05, versus VEH. ##p < 0.01, MDP + LPS versus MDP or FK565 + LPS versus FK565. §§p < 0.01, MDP + LPS or FK565 + LPS versus LPS. Main factor effects without NOD × LPS interactions: ap < 0.01, LPS versus VEH. (D–F): One-way ANOVA: ∗p < 0.05, ∗∗p < 0.01, versus VEH.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

f0020: Effects of MDP (3 mg/kg), FK565 (0.003 mg/kg) and LPS (doses as indicated) on behavior in the OF 21 h post-treatment in male mice. The graphs show the time spent in the central area (A + D), the number of entries into the central area (B + E) and the total distance traveled (C + F) during the 5 min test session. The values are means + SEM, n = 7–8. (A–C): Post-hoc analysis of significant NOD × LPS interactions in 2-way ANOVA: ∗p < 0.05, versus VEH. ##p < 0.01, MDP + LPS versus MDP or FK565 + LPS versus FK565. §§p < 0.01, MDP + LPS or FK565 + LPS versus LPS. Main factor effects without NOD × LPS interactions: ap < 0.01, LPS versus VEH. (D–F): One-way ANOVA: ∗p < 0.05, ∗∗p < 0.01, versus VEH.
Mentions: The behavior in the OF was modified by MDP, FK565 and LPS in a compound-, combination- and time-dependent manner (Fig. 4). The OF test was used to assess anxiety-like behavior as deduced from the time spent in the central area and the entries made to the central area of the OF and locomotion as deduced from the traveling distance (Fig. 4). In experiments with the higher dose of LPS (0.83 mg/kg), two-way ANOVA revealed a significant NOD × LPS interaction for the changes in locomotion (F(2,42) = 3.168, p ⩽ 0.05). Post-hoc analysis showed that while the NOD agonists did not impact on locomotion, treatment with LPS (0.83 mg/kg) slightly decreased the traveling distance in the OF (Fig. 4C). Furthermore, combined treatment with MDP (3 mg/kg) + LPS (0.83 mg/kg) or FK565 (0.003 mg/kg) + LPS (0.83 mg/kg) further diminished the distance traveled when compared with LPS alone, or MDP and FK565, respectively (Fig. 4C). The entries made into the center of the field depended on LPS (F(1,42) = 31.001, p < 0.001), while the effect of the NOD agonists and their interaction with LPS did not reach significance (Fig. 4B). The time spent in the central area of the OF was not significantly affected by any of the compounds (Fig. 4A).

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