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In this review, we summarize and discuss recent studies on structural plasticity changes, particularly apoptosis, in the mammalian hippocampus in relation to stress and depression. Apoptosis continues to occur, yet with very low numbers, in the adult hippocampal dentate gyrus (DG) of various species. Stress and steroid exposure modulate the rate of apoptosis in the DG. Contrary to earlier studies, the impact of chronic stress on structural parameters of the hippocampus like cell number and volume, is rather modest, and requires prolonged and severe stress exposure before only small reductions (< 10 %) become detectable. This does not exclude other structural parameters, like synaptic terminal structure, or dendritic arborization from being significantly altered in critical hippocampal subregions like the DG and/or CA3. Neither does it imply that the functional implications of the changes after stress are also modest. Of interest, most of the structural plasticity changes appear transient and are generally reversible after appropiate recovery periods, or following cessation or blockade of the stress or corticosteroid exposure. The temporary slowing down of both apoptosis and adult proliferation, i.e. the DG turnover, after chronic stress will affect the overall composition, average age and identity of DG cells, and will have considerable consequences for the connectivity, input and properties of the hippocampal circuit and thus for memory function. Modulation of apoptosis and neurogenesis, by drugs interfering with stress components like MR and/or GR, and/or mediators of the cell death cascade, may therefore provide important drug targets for the modulation of mood and memory.

Stress can be a threat to the physiological and psychological integrity of an individual and may result in psychic and behavioral changes. The stress response is mediated through in-concert activity of many brain areas and there is experimental evidence that stress induces structural changes in neuronal networks, in particular in the hippocampus, the prefrontal cortex and the amygdala. Within the hippocampal formation, stress exposure results in remodeling of dendrites of the CA3 pyramidal neurons and in reduced numbers of synapses on these neurons. Furthermore, stress inhibits adult neurogenesis in the dentate gyrus and appears to modulate the GABAergic system. In the prefrontal cortex, repeated exposure to stress causes dendritic retraction and loss of spines in pyramidal neurons whereas in the amygdala stress can elicit dendritic hypertrophy. These microscopically detectable changes in neuronal structures indicate the reorganization of neuronal networks. Moreover, molecular studies show that stress modulates expression of genes involved in neuronal differentiation and/or structural remodeling. Since a wealth of data documents the adverse effects of stress on emotions and cognition these alterations are commonly interpreted as the deleterious effect of chronic stress on the central nervous system. However, it is also possible that at least part of these changes reflect adaptive responses, as the network system rearranges its connections in order to cope with the changing requirements from the internal or external environment.