Escitalopram affects cytoskeleton and synaptic plasticity pathways in a rat gene-environment interaction model of depression as revealed by proteomics. Part II: environmental challenge.

Large-scale investigations aimed at elucidating the molecular mechanism of action of antidepressant treatment are achievable through the application of proteomic technologies. We performed a proteomic study on the Flinders Sensitive Line (FSL), a genetically selected rat model of depression, and the control Flinders Resistant Line (FRL). To evaluate gene-environment interactions, FSL and FRL animals were separated from their mothers for 3 h from postnatal days 2 to 14 (maternal separation; MS), since early-life trauma is considered an important antecedent of depression. All groups received either escitalopram (Esc) admixed to food pellets (25 mg/kg.d) or vehicle for 1 month. Protein extracts from prefrontal/frontal cortex and hippocampus were separated by 2D electrophoresis. Proteins differentially modulated were identified by mass spectrometry. Bioinformatics analyses were performed to discover gene ontology terms associated with the modulated proteins. This paper was focused on the modifications induced by the environmental challenge of MS, both on the predisposed genetic background and on the resistant phenotype. The combination between Esc treatment and MS was investigated by comparing the MS, Esc-treated rats with rats subjected to each single procedure. In MS rats, antidepressant treatment influenced mainly proteins involved in carbohydrate metabolism in FSL rats and in vesicle-mediated transport in FRL rats. When studying the interaction between Esc and MS vs. non-separated rats, proteins playing a role in cytoskeleton organization, neuronal development, vesicle-mediated transport and synaptic plasticity were identified. The results provide further support to the available reports that antidepressant treatment affects intracellular pathways and also suggest new potential targets for future therapeutic intervention.