Proteomics of Preclinical Models of Depression

Major depressive disorder (MDD) is a widespread and disabling disease whose aetiology and pathophysiological basis are still incompletely understood. In this review, hypothesis-free proteomic analyses carried out on animal models of MDD to study the neurobiological correlates of MDD are described and discussed. Most proteomic investigations rely on the induction of depression-like behaviours via exposure to stressful experiences, similarly to known mechanisms of MDD occurrence. Animal models included exposure to chronic corticosterone treatment, prenatal restraint stress, earlylife stress, chronic mild stress, restraint stress and social defeat, as well as the induction of learned helplessness and analysis of genetically selected strains. In other instances, models of anxiety behaviours were examined, since anxiety disorders are often associated with MDD. Although proteomic analyses made use of different technologies, in most instances protein separation was achieved by means of gel electrophoresis. The majority of the studies were performed on brain regions allegedly affected in MDD patients, such as the hippocampus, prefrontal cortex, amygdala and hypothalamus. Proteins connected to different biochemical functions were modulated in the distinct animal models and brain regions, while, in some cases, the comprehensive impact on signaling pathways was evaluated as well. Globally, a large number of different proteins were identified in the proteomic experiments, although a methodological bias for water-soluble abundant proteins should be appreciated. Subsequent approaches should be adopted to validate, interpret and exploit more extensively the vast amount of information produced. The results summarised in this review provide potential new avenues for the investigation of the molecular neurobiology of MDD.