Pharmacoproteomic investigation into antidepressant response in two mouse inbred strains.
Summary of "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 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 2 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, two dimensional polyacrylamide gel electrophoresis (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 3 gene products involved in serotonergic (PXBD5, YHWAB, SLC25A4) and one in noradrenergic antidepressant action (PXBD6).
King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, UK.
This article was published in the following journal.
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22696452
- DOI: http://dx.doi.org/10.1002/pmic.201100306
Medical and Biotech [MESH] Definitions
Mice, Inbred Mrl Lpr
A mouse substrain that is genetically predisposed to the development of systemic lupus erythematosus-like syndrome, which has been found to be clinically similar to the human disease. It has been determined that this mouse strain carries a mutation in the fas gene. Also, the MRL/lpr is a useful model to study behavioral and cognitive deficits found in autoimmune diseases and the efficacy of immunosuppressive agents.
Mice, Inbred Strains
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
Animals, Inbred Strains
Animals produced by the mating of littermates or siblings over multiple generations. The resultant strain of animals is virtually identical genotypically. Highly inbred animal lines allow the study of certain traits in a relatively pure form. (Segen, Dictionary of Modern Medicine, 1992)
An outbred strain of rats developed in 1915 by crossing several Wistar Institute white females with a wild gray male. Inbred strains have been derived from this original outbred strain, including Long-Evans cinnamon rats (RATS, INBRED LEC) and Otsuka-Long-Evans-Tokushima Fatty rats (RATS, INBRED OLETF), which are models for Wilson's disease and non-insulin dependent diabetes mellitus, respectively.
Transplantation between genetically identical individuals, i.e., members of the same species with identical histocompatibility antigens, such as monozygotic twins, members of the same inbred strain, or members of a hybrid population produced by crossing certain inbred strains.
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