2004 Route 28 Summit Topic
Adult Neurogenesis and Neuropsychiatric Disorders
The adult brain can generate new neurons, but it normally does so only in two privileged regions. One of these is the hippocampus, which plays a central role in learning and memory processes and which is affected in many neuropsychiatric disorders including dementias, depression, temporal lobe epilepsy and others.
We will discuss how stem cells and adult neurogenesis might contribute to malfunction of the central nervous system and how one might use the stem cell's inherent potential for regeneration in order to overcome such conditions of disturbed neuroplasticity. Some of the most accomplished experts from the field have agreed to talk at Route28 in 2004 and an extraordinary spectrum of expertise and up-to-date information will be made accessible to the students.
A controversial, but highly stimulating theory has tried to link a failure of adult hippocampal neurogenesis to the pathogenesis of major depression. The hypothesis has already sparked many fruitful discussions, specifically dedicated symposia at larger conferences and a number of very instructive new experiments. Independent of whether or not the theory will turn out to be true it is an idea that has clearly advanced the field. Route28 in 2004 will use the example of the neurogenesis hypothesis of depression to ask questions dealing with the potential contribution of stem cells (as the source of adult neurogenesis) and newly generated neurons (as the product of adult neurogenesis) to brain function in health and disease.
Adult neurogenesis has evolved from a chance observation to a core question in brain plasticity. Can the brain function-dependently alter its structure on the level of entire nerve cells? The concept of "plasticity" has revolutionized neurobiology, but it has long been assumed that plasticity only affected glial cells and the processes and synapses of neurons, not the number of neurons.
Despite many years of intensive research on psychiatric disorders such as major depression, schizophrenia, autism and others, no conclusive structural correlate has been found for these conditions. One potential explanation for this could be that the structural changes do not manifest themselves in gross anatomical abnormalities but in more subtle disturbances of plasticity. Adult neurogenesis would not necessarily have to be at the center of such new concepts, but it might just be the most conspicuous example of altered structural plasticity. In the public perception stem cell biology is important because of the novel types of cell-based therapy that appear to be within reach when stem cells could be used. At the Route28 meeting in 2002 we have focused on cell replacement therapies and organized the meeting around the example of Parkinson's disease. In 2004 we will address the other face of neural stem cell biology. How are stem cells involved in normal and diseased brain function? We will use major depression as the anchor point for this endeavor, but will include the consideration of other diseases, most notably schizophrenia. What are the implications of neural stem cell biology and adult neurogenesis for our understanding of these disorders? Could novel therapies be based on the idea that disturbed cellular plasticity underlies the clinical condition?
To maintain a clear focus of the workshop we will not discuss addiction and drug abuse in 2004, because the complexity of this topic would justify a workshop of its own and because the available data on cellular plasticity in animal models of addiction are still too scarce.