Chronic stress, depression and antidepressants: effects on gene transcription in the hippocampus

Depressive disorders are among the most frequent forms of mental illness. Both genetic and environmental factors, such as stress, are involved in the etiology of depression. Therefore, chronic stress paradigms in laboratory animals constitute an important tool for research in this field. The molecular bases of chronic stress/depression are largely unknown, although a large amount of information has been accumulated during recent years. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis as well as structural and physiological alterations in the hippocampus and neocortex are known to occur. Modifications in the expression level of some genes, such as brain-derived neurotrophic factor, cAMP-response-element binding protein, serotonin receptors and HPA axis components were consistently associated in a number of experimental models. However, recent results suggest that several synaptic proteins, transcription factors and proteins involved in neuronal growth/differentiation, are also modified in their expression in experimental models of chronic stress. In general, these alterations can be reversed by treatment with antidepressants. Thus, a complex pattern of gene expression leading to stress/depression is starting to emerge. We summarize here recent findings on the alterations of gene expression in the hippocampus of chronically stressed and antidepressant treated animals.