Signals for regeneration

It begins almost imperceptibly, initially with unspecific symptoms. Many of those affected have bouts of depression and withdraw from their friends. When their physical mobility is later impeded, demonstrated for example by their handwriting, this is indeed an indication of Parkinson's Disease. The symptoms occur because certain neurons in the brain die off. These cells produce the neurotransmitter dopamine, which is responsible for controlling motor skills. When the first signs of the disease become noticeable, 50 to 60 per cent of these cells will already have died. And this loss continues, resulting in the patients becoming even less mobile.

"Our long-term goal is to influence stem cells in the brain in such a way that they replace the dopamine-producing cells," says Dr. Dieter Chichung Lie from the GSF-National Research Centre for Environment and Health in Munich. The neuroscientist's research team has already been able to show that stem cells exist in the affected part of the brain, the so-called substantia nigra. Even in adults, these cells are still capable of dividing and forming various kinds of nerve cells. Up to the 1990s, it had, by contrast, been assumed that this was only possible during embryonic development and shortly after birth. However, the stem cells identified by Lie's group only form certain types of brain cells. These are unable to balance out the lack of dopamine in the affected brain region. In experiments with stem cell cultures, the researchers succeeded in influencing the cells' development to such an extent that they at least showed some characteristics of dopamine-producing cells. Lie's main interest is in the question of what signals instruct the stem cells in the brain to form new neurons or to continue to remain dormant. With his Young Investigators Group he is studying how a certain family of proteins called "Wnt" control stem cells in the adult brain. Their recent results suggest that the Wnt proteins both keep stem cells dormant and provide the signal for them to mature. The important question is now to understand how Wnt proteins can influence such opposing processes.

In the organism, signals for rest and maturation have to be closely coordinated. The function of the hippocampus, a brain structure with a central role in learning and memory formation, seems to depend on the generation of new neurons from stem cells. For example, if the number of new neurons is low this can negatively affect learning and memory performance. If, on the other hand, too many stem cells develop, the reserves are exhausted too quickly. In addition, stronger cell division could also result in tumours developing. The balance between rest and generation of new neurons from stem cells may also be crucial for the treatment of diseases like Parkinson's or Alzheimer's that involve the loss of brain cells. The possibility of getting the existing stem cells to replace the damaged neurons would be a starting point for a new therapy against these presently incurable diseases.