Pharmacoproteomic investigation into antidepressant response in two mouse inbred strains

Karim Malki, James Campbell, Matthew Davies, Robert Keers, Rudolf Uher, Malcolm Ward, Jose Paya-Cano, Katherine J. Aitchinson, Elke Binder, Frans Sluyter, Karsten Kuhn, Stefan Selzer, Ian Craig, Peter McGuffin, Leonard C. Schalkwyk

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


In this study, we present a pharmacoproteomic investigation of response to antidepressants two inbred strains. Our aim was to uncover molecular mechanisms underlying antidepressant action and identify new biomarkers to determine therapeutic response to two antidepressants with proven efficacy in the treatment of depression but divergent mechanisms of action. Mice were treated with the pro-noradrenergic drug nortriptyline, the pro-serotonergic drug escitalopram or saline. Quantitative proteomic analyses were undertaken on hippocampal tissue from a study design that used two inbred mouse strains, two depressogenic protocols and a control condition, (maternal separation, chronic mild stress, control), two antidepressant drugs and two dosing protocols. The proteomic analysis was aimed at the identification of specific drug-response markers. Complementary approaches, 2DE and isobaric tandem mass tagging (TMT), were applied to the selected experimental groups. To investigate the relationship between proteomic profiles, depressogenic protocols and drug response, 2DE and TMT data sets were analysed using multivariate methods. The results highlighted significant strain- and stress-related differences across both 2DE and TMT data sets and identified the three gene products involved in serotonergic (PXBD5, YHWAB, SLC25A4) and one in noradrenergic antidepressant action (PXBD6).

Original languageEnglish
Pages (from-to)2355-2365
Number of pages11
Issue number14
Publication statusPublished - Aug 2012


  • 14-3-3 Proteins
  • Adenine Nucleotide Translocator 1
  • Animals
  • Antidepressive Agents
  • Citalopram
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Hippocampus
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Multivariate Analysis
  • Nortriptyline
  • Peroxiredoxins
  • Principal Component Analysis
  • Proteome
  • Proteomics
  • Reproducibility of Results
  • Stress, Psychological
  • Tandem Mass Spectrometry
  • Weaning


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