Why new neurons? Possible functions for adult hippocampal neurogenesis.
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Biomedical subjects
Publications and source records attributed to Gerd Kempermann.
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Neurons are continually born from endogenous stem cells and added to the dentate gyrus throughout life, but adult hippocampal neurogenesis declines precipitously with age. Short-term exposure to an enriched environment leads to a striking increase in new neurons, along with a substantial improvement in behavioral performance. Could this plastic response be relevant for explaining the beneficial effects of leading "an active life" on brain function and pathology? Adult hippocampal neurogenesis in mice living in an enriched environment from the age of 10 to 20 months was fivefold higher than in controls. Relatively, the increase in neuronal phenotypes was entirely at the expense of newly generated astrocytes. This cellular plasticity occurred in the context of significant improvements of learning parameters, exploratory behavior, and locomotor activity. Enriched living mice also had a reduced lipofuscin load in the dentate gyrus, indicating decreased nonspecific age-dependent degeneration. Therefore, in mice signs of neuronal aging can be diminished by a sustained active and challenging life, even if this stimulation started only at medium age. Activity exerts not only an acute but also a sustained effect on brain plasticity.
Major depression, whose biological origins have been difficult to grasp for decades, might result from a disturbance in neuronal plasticity. New theories begin to consider a fundamental role of adult hippocampal neurogenesis in this loss of plasticity. Could depression and other mood disorders therefore be 'stem cell disorders'? In this review, the potential role of adult hippocampal neurogenesis and of neuronal stem or progenitor cells in depression is discussed with regard to those aspects that are brought up by recent research on how adult hippocampal neurogenesis is regulated. What is known about this regulation today are mosaic pieces and indicates that regulation is complex and is modulated on several levels. Accordingly, emphasis is here laid on those regulatory feedback mechanisms and interdependencies that could help to explain how the pathogenic progression from a hypothesized disruptive cause can occur and lead to the complex clinical picture in mood disorders. While the 'neurogenic theory' of depression remains highly speculative today, it might stimulate the generation of sophisticated working hypotheses, useful animal experiments and the first step towards new therapeutic approaches.