Depression may be viewed as a disorder of networks that interconnect different brain areas to which predominant roles in the regulation of individual behavioural domains (mood, anxiety, cognition and reward) that contribute to the depressive state have been ascribed. Using an animal model of depression (chronic unpredictable stress) as well as primary neuronal cell cultures, our studies have focused on volumetric and cell number changes (including those resulting from neurogenesis and apoptosis) in the prefrontal cortex and hippocampus, as well as on patterns of dendritic arborization and signs of synaptic plasticity that parallel the manifestation of depressive-like behaviours. They have also begun to cast light on some of the cellular mechanisms underlying these changes; in this respect, insights into the requirements for maintaining synaptic structural and functional integrity have been gained from work with Alzheimer’s disease-related proteins and peptides. Besides identifying potential targets for antidepressant drugs, our studies add support to the network hypothesis of depression.
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