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Behavioral extremes of trait anxiety in mice are characterized by distinct metabolic profiles

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http://pubman.mpdl.mpg.de/cone/persons/resource/persons80323

Filiou,  Michaela D.
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80462

Nussbaumer,  Markus
Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80548

Teplytska,  Larysa
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80418

Landgraf,  Rainer
Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80561

Turck,  Christoph W.
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

Filiou, M. D., Asara, J. M., Nussbaumer, M., Teplytska, L., Landgraf, R., & Turck, C. W. (2014). Behavioral extremes of trait anxiety in mice are characterized by distinct metabolic profiles. JOURNAL OF PSYCHIATRIC RESEARCH, 58, 115-122. doi:10.1016/j.jpsychires.2014.07.019.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0024-475B-5
Abstract
No comprehensive metabolic profile of trait anxiety is to date available. To identify metabolic biosignatures for different anxiety states, we compared mice selectively inbred for similar to 40 generations for high (HAB), normal (NAB) or low (LAB) anxiety-related behavior. Using a mass spectrometry-based targeted metabolomics approach, we quantified the levels of 257 unique metabolites in the cingulate cortex and plasma of HAB, NAB and LAB mice. We then pinpointed affected molecular systems in anxiety-related behavior by an in silico pathway and network prediction analysis followed by validation of in silico predicted alterations with molecular assays. We found distinct metabolic profiles for different trait anxiety states and detected metabolites with altered levels both in cingulate cortex and plasma. Metabolomics data revealed common candidate biomarkers in cingulate cortex and plasma for anxiety traits and in silico pathway analysis implicated amino acid metabolism, pyruvate metabolism, oxidative stress and apoptosis in the regulation of anxiety-related behavior. We report characteristic biosignatures for trait anxiety states and provide a network map of pathways involved in anxiety-related behavior. Pharmacological targeting of these pathways will enable a mechanism-based approach for identifying novel therapeutic targets for anxiety disorders. (C) 2014 Elsevier Ltd. All rights reserved.