Effect of an anti-depressant on mouse hippocampus protein turnover using MIMS.

Although antidepressants have been used in the treatment of affective disorders for over fifty years, the precise mechanism of their action remains unknown. Treatment regimens are based by and large on empirical parameters and characterized by a trial and error scheme. A better understanding of the mechanisms involved in antidepressant drug response is of fundamental importance for the development of new compounds that have a higher success rate and specificity. In order to elucidate the molecular pathways involved in the action of antidepressants, we wish to identify brain areas, cell types, and organelles that are targeted by antidepressant treatment in mice. Multi-isotope Imaging Mass Spectrometry (MIMS) allows a quantitative approach to this analysis, allowing us to delineate antidepressant effect on protein synthesis in the brain at single cell and organelle resolution. In these experiments, we obtained a global analysis of protein turnover in the hippocampus dentate gyrus (DG) and in the Cornu Ammonis (CA) regions, together with a subcellular analysis in the granular cells and others.