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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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Experimental groups and time lines. In protocol 1, the effects of the PRR agonists on daily activity were assessed in the LabMaster system. In protocol 2, the effects of MDP and FK565 alone and the combination of MDP or FK565 with the higher dose of LPS (0.83 mg/kg) on sickness and central c-Fos expression were evaluated. In protocol 3, the effects of MDP and FK565 alone and the combination of MDP or FK565 with the lower dose of LPS (0.1 mg/kg) on sickness, mood and inflammation-related parameters were analyzed. Time zero represents the time of injection and was consistent across all experiments. Abbreviations: CORT = corticosterone, KYN/TRP = kynurenine/tryptophan ratio, FST = forced swim test, OF = open field, Temp = temperature, TST = tail suspension test.
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f0005: Experimental groups and time lines. In protocol 1, the effects of the PRR agonists on daily activity were assessed in the LabMaster system. In protocol 2, the effects of MDP and FK565 alone and the combination of MDP or FK565 with the higher dose of LPS (0.83 mg/kg) on sickness and central c-Fos expression were evaluated. In protocol 3, the effects of MDP and FK565 alone and the combination of MDP or FK565 with the lower dose of LPS (0.1 mg/kg) on sickness, mood and inflammation-related parameters were analyzed. Time zero represents the time of injection and was consistent across all experiments. Abbreviations: CORT = corticosterone, KYN/TRP = kynurenine/tryptophan ratio, FST = forced swim test, OF = open field, Temp = temperature, TST = tail suspension test.

Mentions: Three different protocols were used (Fig. 1). For details on the choice of dosing and timing of injections see Sections 2.7 “Dosing” and 2.8 “Timing of injections”.


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)

Experimental groups and time lines. In protocol 1, the effects of the PRR agonists on daily activity were assessed in the LabMaster system. In protocol 2, the effects of MDP and FK565 alone and the combination of MDP or FK565 with the higher dose of LPS (0.83 mg/kg) on sickness and central c-Fos expression were evaluated. In protocol 3, the effects of MDP and FK565 alone and the combination of MDP or FK565 with the lower dose of LPS (0.1 mg/kg) on sickness, mood and inflammation-related parameters were analyzed. Time zero represents the time of injection and was consistent across all experiments. Abbreviations: CORT = corticosterone, KYN/TRP = kynurenine/tryptophan ratio, FST = forced swim test, OF = open field, Temp = temperature, TST = tail suspension test.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

f0005: Experimental groups and time lines. In protocol 1, the effects of the PRR agonists on daily activity were assessed in the LabMaster system. In protocol 2, the effects of MDP and FK565 alone and the combination of MDP or FK565 with the higher dose of LPS (0.83 mg/kg) on sickness and central c-Fos expression were evaluated. In protocol 3, the effects of MDP and FK565 alone and the combination of MDP or FK565 with the lower dose of LPS (0.1 mg/kg) on sickness, mood and inflammation-related parameters were analyzed. Time zero represents the time of injection and was consistent across all experiments. Abbreviations: CORT = corticosterone, KYN/TRP = kynurenine/tryptophan ratio, FST = forced swim test, OF = open field, Temp = temperature, TST = tail suspension test.
Mentions: Three different protocols were used (Fig. 1). For details on the choice of dosing and timing of injections see Sections 2.7 “Dosing” and 2.8 “Timing of injections”.

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