Neurogenesis in the adult brain: is there an association with mental disorders?

Abstract

Within the last two decades, our view of the mature mammalian brain has changed. The brain is far from being fixed and immutable, as a multitude of factors such as environmental stimulation, learning, growth factors, glucocorticoids and sexual hormones, stress, aging, and neurotransmitters such as glutamate and serotonin regulate generation of new neurons; also many drugs have an impact on neurogenesis in selected brain regions such as the subgranular zone of the hippocampal dentate gyrus and the subventricular zone of the lateral ventricles. This newfound capacity has forced a new look at plasticity of the brain, an organ previously considered to have a stable structure. The term neural plasticity summarizes dynamic processes that constitute the capacity of neural systems, single neurons, glia cells, synapses, receptors, and other components to adapt and change their structural or functional repertoire in response to alterations in the internal and/or external environment. Neural plasticity is mandatory for adequate functioning of an individual in the continuously changing environment. However, as demonstrated e.g., in brains of patients with mood disorders it became clear that neural plastic processes are not always beneficial. The discovery of stem cells in the adult brain and of adult neurogenesis has added new dimensions to neuroplasticity research. Moreover, it raises questions regarding the underlying mechanisms of the newly generated neurons, and how they influence the functioning of established neuronal networks. The magnitude and ubiquity of adult neurogenesis across vertebrates suggests that it is an essential process and not merely a residue of development. The functional implications of adult neurogenesis are still a matter of debate, but several reports provide evidence, although so far only correlational, that neurogenesis in the adult dentate gyrus might be involved in learning and memory processes. Moreover, new theories have linked neuropsychiatric disorders such as depression, schizophrenia, dementia, and drug addiction to a failure of adult neurogenesis. The hippocampus is one of the brain structures that has been extensively studied with regard to the consequences of stress, depression, and antidepressant actions. Recent imaging studies in humans revealed that the hippocampus undergoes selective volume reduction in stress-related neuropsychiatric disorders such as recurrent depressive illness. Today there is compelling experimental evidence that reduced dentate neurogenesis and hippocampal volume loss in animal models of depression can be reversed by antidepressant treatment. These findings caused the formulation of the novel concept that reduced neurogenesis may contribute to the pathogenesis of depression. However, the exact mechanisms responsible for the hippocampal volume loss in major depression are so far unclear. In their article Czeh and Lucassen state that neuronal loss can be excluded as cause for the volume loss. As apoptosis and reduced neurogenesis contribute only to a very limited extent to the observed volume loss other factors such as alterations in the glial, dendritic, axonal, and synaptic compartments are discussed to contribute to the hippocampal shrinkage. Together with shifts in both the extracellular space and fluid volume theses factors may provide a mechanistic explanation for the obE. Fuchs (&) Clinical Neurobiology Laboratory German Primate Center Kellnerweg 4 37077 Goettingen, Germany Tel.: +49-551/385-1130 E-Mail: efuchs@gwdg.de