Pharmacoproteomic investigation into antidepressant response in two mouse inbred strains

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...

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Bibliographic Details
Published in:	Proteomics (Weinheim) Vol. 12; no. 14; pp. 2355 - 2365
Main Authors:	Malki, Karim, Campbell, James, Davies, Matthew, Keers, Robert, Uher, Rudolf, Ward, Malcolm, Paya-Cano, Jose, Aitchinson, Katherine J., Binder, Elke, Sluyter, Frans, Kuhn, Karsten, Selzer, Stefan, Craig, Ian, McGuffin, Peter, Schalkwyk, Leonard C.
Format:	Journal Article
Language:	English
Published:	Weinheim Blackwell Publishing Ltd 01-08-2012 Wiley-VCH Wiley Subscription Services, Inc
Subjects:	14-3-3 Proteins - genetics 14-3-3 Proteins - metabolism Adenine Nucleotide Translocator 1 - genetics Adenine Nucleotide Translocator 1 - metabolism Analytical, structural and metabolic biochemistry Animal proteomics Animals Antidepressants Antidepressive Agents - pharmacology Biological and medical sciences Citalopram - pharmacology Electrophoresis, Gel, Two-Dimensional Escitalopram Female Fundamental and applied biological sciences. Psychology GENDEP Hippocampus - chemistry Hippocampus - drug effects Hippocampus - metabolism Male Medical research Mice Mice, Inbred C57BL Mice, Inbred Strains Miscellaneous Multivariate Analysis Nortriptyline Nortriptyline - pharmacology Peroxiredoxins - genetics Peroxiredoxins - metabolism Pharmacoproteomics Principal Component Analysis Proteins Proteome - analysis Proteome - drug effects Proteomics Reproducibility of Results Rodents Stress, Psychological - drug therapy Tandem Mass Spectrometry Weaning Nortriptyline Vertebrata Mammalia Animal proteomics Mouse Escitalopram Antidepressants Rodentia Proteomics GENDEP Pharmacoproteomics Strain
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Summary:	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).
Bibliography:	ArticleID:PMIC7148 European Commission Framework 6 - No. LSHB-CT-2003-503428 National Institute for Health Research, Department of Health, United Kingdom istex:CCFEF48869F24BF6C3690AD145D38B1756A1ACBD ark:/67375/WNG-L13ZD9ZG-B See the article online to view Figs. 3–6 in colour. Colour Online ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	1615-9853 1862-8346 1615-9861
DOI:	10.1002/pmic.201100306