title: Proteomic and metabolomic profiling of a trait anxiety mouse model implicate affected pathways.
abstract: Depression and anxiety disorders affect a great number of people worldwide. Whereas singular factors have been associated with the pathogenesis of psychiatric disorders, growing evidence emphasizes the significance of dysfunctional neural circuits and signaling pathways. Hence, a systems biology approach is required to get a better understanding of psychiatric phenotypes such as depression and anxiety. Furthermore, the availability of biomarkers for these disorders is critical for improved diagnosis and monitoring treatment response. In the present study, a mouse model presenting with robust high versus low anxiety phenotypes was subjected to thorough molecular biomarker and pathway discovery analyses. Reference animals were metabolically labeled with the stable (15)N isotope allowing an accurate comparison of protein expression levels between the high anxiety-related behavior versus low anxiety-related behavior mouse lines using quantitative mass spectrometry. Plasma metabolomic analyses identified a number of small molecule biomarkers characteristic for the anxiety phenotype with particular focus on myo-inositol and glutamate as well as the intermediates involved in the tricarboxylic acid cycle. In silico analyses suggested pathways and subnetworks as relevant for the anxiety phenotype. Our data demonstrate that the high anxiety-related behavior and low anxiety-related behavior mouse model is a valuable tool for anxiety disorder drug discovery efforts.
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Yaoyang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Michaela D
authors.initials: MD
authors.lastname: Filiou
authors.forename: Stefan
authors.initials: S
authors.lastname: Reckow
authors.forename: Philipp
authors.initials: P
authors.lastname: Gormanns
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Maccarrone
authors.forename: Melanie S
authors.initials: MS
authors.lastname: Kessler
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Frank
authors.forename: Boris
authors.initials: B
authors.lastname: Hambsch
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Rainer
authors.initials: R
authors.lastname: Landgraf
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Turck
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001008:Anxiety Disorders / Q000097:blood* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D024402:Carbonic Anhydrase II / Q000097:blood / Q000737:chemistry; D018698:Glutamic Acid / Q000097:blood; D006624:Hippocampus / Q000201:enzymology; D007294:Inositol / Q000097:blood; D007791:Lactoylglutathione Lyase / Q000737:chemistry / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D008969:Molecular Sequence Data; D020412:Multifactorial Inheritance; D010446:Peptide Fragments / Q000737:chemistry; D011228:Prealbumin / Q000737:chemistry / Q000378:metabolism; D040081:Protein Array Analysis; D040901:Proteomics; D000683:Serum Amyloid P-Component / Q000737:chemistry / Q000378:metabolism
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011228:Prealbumin; D000683:Serum Amyloid P-Component; D018698:Glutamic Acid; D007294:Inositol; D024402:Carbonic Anhydrase II; D007791:Lactoylglutathione Lyase