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), LPS (0.83 mg/kg) and MDP + LPS on c-Fos expression 3 h after treatment of male mice. Mice were injected i.p. with saline (VEH), MDP, LPS or MDP + LPS. Brains were collected 3 h post-treatment and the expression of c-Fos, a marker of neuronal activation, was measured by immunohistochemistry. The values are means + SEM, n = 3–5. Post-hoc analysis of significant NOD × LPS interactions in 2-way ANOVA: ∗p < 0.05, ∗∗p < 0.01, versus VEH. ##p < 0.01, MDP + LPS versus MDP. §p < 0.05, §§p < 0.01, MDP + LPS versus LPS. Main factor effects without NOD × LPS interactions: ap < 0.01, LPS versus VEH. bp < 0.01, NLR agonist versus VEH. Abbreviations: BNSTd/v = bed nucleus of the stria terminalis dorsal/ventral, CeA = central amygdala, DG = dentate gyrus, PVN = paraventricular nucleus of the hypothalamus, SFO = subfornical organ, SO = supraoptic nucleus.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

f0040: Effects of MDP (3 mg/kg), LPS (0.83 mg/kg) and MDP + LPS on c-Fos expression 3 h after treatment of male mice. Mice were injected i.p. with saline (VEH), MDP, LPS or MDP + LPS. Brains were collected 3 h post-treatment and the expression of c-Fos, a marker of neuronal activation, was measured by immunohistochemistry. The values are means + SEM, n = 3–5. Post-hoc analysis of significant NOD × LPS interactions in 2-way ANOVA: ∗p < 0.05, ∗∗p < 0.01, versus VEH. ##p < 0.01, MDP + LPS versus MDP. §p < 0.05, §§p < 0.01, MDP + LPS versus LPS. Main factor effects without NOD × LPS interactions: ap < 0.01, LPS versus VEH. bp < 0.01, NLR agonist versus VEH. Abbreviations: BNSTd/v = bed nucleus of the stria terminalis dorsal/ventral, CeA = central amygdala, DG = dentate gyrus, PVN = paraventricular nucleus of the hypothalamus, SFO = subfornical organ, SO = supraoptic nucleus.

Mentions: A similar picture emerged for the circulating levels of kynurenine (Fig. 7D). Kynurenine levels were increased by LPS, MDP + LPS and FK565 + LPS (F(3,26) = 12.098, p < 0.001). As for the kynurenine/tryptophan ratio, the kynurenine levels in the MDP + LPS group were significantly higher than in the LPS group, while the levels in the FK565 + LPS group were increased by trend only compared to LPS alone (p = 0.077). The levels of tryptophan were increased by MDP + LPS and FK565 + LPS, while LPS alone did not change the plasma tryptophan levels (F(3,26) = 11.207, p < 0.001) (Fig. 8E). Furthermore, the tryptophan levels in the FK565 + LPS group were significantly higher than in the LPS group.


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), LPS (0.83 mg/kg) and MDP + LPS on c-Fos expression 3 h after treatment of male mice. Mice were injected i.p. with saline (VEH), MDP, LPS or MDP + LPS. Brains were collected 3 h post-treatment and the expression of c-Fos, a marker of neuronal activation, was measured by immunohistochemistry. The values are means + SEM, n = 3–5. Post-hoc analysis of significant NOD × LPS interactions in 2-way ANOVA: ∗p < 0.05, ∗∗p < 0.01, versus VEH. ##p < 0.01, MDP + LPS versus MDP. §p < 0.05, §§p < 0.01, MDP + LPS versus LPS. Main factor effects without NOD × LPS interactions: ap < 0.01, LPS versus VEH. bp < 0.01, NLR agonist versus VEH. Abbreviations: BNSTd/v = bed nucleus of the stria terminalis dorsal/ventral, CeA = central amygdala, DG = dentate gyrus, PVN = paraventricular nucleus of the hypothalamus, SFO = subfornical organ, SO = supraoptic nucleus.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

f0040: Effects of MDP (3 mg/kg), LPS (0.83 mg/kg) and MDP + LPS on c-Fos expression 3 h after treatment of male mice. Mice were injected i.p. with saline (VEH), MDP, LPS or MDP + LPS. Brains were collected 3 h post-treatment and the expression of c-Fos, a marker of neuronal activation, was measured by immunohistochemistry. The values are means + SEM, n = 3–5. Post-hoc analysis of significant NOD × LPS interactions in 2-way ANOVA: ∗p < 0.05, ∗∗p < 0.01, versus VEH. ##p < 0.01, MDP + LPS versus MDP. §p < 0.05, §§p < 0.01, MDP + LPS versus LPS. Main factor effects without NOD × LPS interactions: ap < 0.01, LPS versus VEH. bp < 0.01, NLR agonist versus VEH. Abbreviations: BNSTd/v = bed nucleus of the stria terminalis dorsal/ventral, CeA = central amygdala, DG = dentate gyrus, PVN = paraventricular nucleus of the hypothalamus, SFO = subfornical organ, SO = supraoptic nucleus.
Mentions: A similar picture emerged for the circulating levels of kynurenine (Fig. 7D). Kynurenine levels were increased by LPS, MDP + LPS and FK565 + LPS (F(3,26) = 12.098, p < 0.001). As for the kynurenine/tryptophan ratio, the kynurenine levels in the MDP + LPS group were significantly higher than in the LPS group, while the levels in the FK565 + LPS group were increased by trend only compared to LPS alone (p = 0.077). The levels of tryptophan were increased by MDP + LPS and FK565 + LPS, while LPS alone did not change the plasma tryptophan levels (F(3,26) = 11.207, p < 0.001) (Fig. 8E). Furthermore, the tryptophan levels in the FK565 + LPS group were significantly higher than in the LPS group.

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