title: Proteomics and metabolomics analysis of a trait anxiety mouse model reveals divergent mitochondrial pathways.
abstract: BACKGROUND
  Although anxiety disorders are the most prevalent psychiatric disorders, no molecular biomarkers exist for their premorbid diagnosis, accurate patient subcategorization, or treatment efficacy prediction. To unravel the neurobiological underpinnings and identify candidate biomarkers and affected pathways for anxiety disorders, we interrogated the mouse model of high anxiety-related behavior (HAB), normal anxiety-related behavior (NAB), and low anxiety-related behavior (LAB) employing a quantitative proteomics and metabolomics discovery approach.
  
  
  METHODS
  We compared the cingulate cortex synaptosome proteomes of HAB and LAB mice by in vivo (15)N metabolic labeling and mass spectrometry and quantified the cingulate cortex metabolomes of HAB/NAB/LAB mice. The combined data sets were used to identify divergent protein and metabolite networks by in silico pathway analysis. Selected differentially expressed proteins and affected pathways were validated with immunochemical and enzymatic assays.
  
  
  RESULTS
  Altered levels of up to 300 proteins and metabolites were found between HAB and LAB mice. Our data reveal alterations in energy metabolism, mitochondrial import and transport, oxidative stress, and neurotransmission, implicating a previously nonhighlighted role of mitochondria in modulating anxiety-related behavior.
  
  
  CONCLUSIONS
  Our results offer insights toward a molecular network of anxiety pathophysiology with a focus on mitochondrial contribution and provide the basis for pinpointing affected pathways in anxiety-related behavior.
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstrasse 2, Munich, Germany.
authors.forename: Michaela D
authors.initials: MD
authors.lastname: Filiou
authors.forename: Yaoyang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Larysa
authors.initials: L
authors.lastname: Teplytska
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: Elisabeth
authors.initials: E
authors.lastname: Frank
authors.forename: Melanie S
authors.initials: MS
authors.lastname: Kessler
authors.forename: Boris
authors.initials: B
authors.lastname: Hambsch
authors.forename: Markus
authors.initials: M
authors.lastname: Nussbaumer
authors.forename: Mirjam
authors.initials: M
authors.lastname: Bunck
authors.forename: Tonia
authors.initials: T
authors.lastname: Ludwig
authors.forename: Alexander
authors.initials: A
authors.lastname: Yassouridis
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: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology; D002952:Citric Acid Cycle / Q000235:genetics; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways / Q000235:genetics; D055432:Metabolomics; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009587:Nitrogen Isotopes / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D040901:Proteomics; D009435:Synaptic Transmission / Q000235:genetics; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D000975:Antioxidants; D009587:Nitrogen Isotopes