In mice the researchers inactivated the receptors of two neurotrophic factors in the substantia nigra, an area in which early cell death gives rise to Parkinson disease. The brains of these mice developed normally, however in the adult animal a significant decrease of dopaminergic neurons was observed over time, similar to what is seen in patients suffering form Parkinson disease. (PLoS Biology, March 5, 2007).
Parkinson patients suffer from loss of dopaminergic neurons in a certain region of the brain, the substantia nigra. Several experiments seem to indicate that the neurotrophic factor GDNF and its receptor might prevent an early, uncontrolled death of these neurons. The international team consisting of Edgar Kramer, Liviu Aron, Sabine Seitz und Rdiger Klein of the Max Planck Institute of Neurobiology has now shown that neurons of the substantia nigra lacking the Ret-receptor indeed suffer an earlier death compared to normal control neurons. Loss of nerve cells and axons in this brain region is typical for Parkinson disease.
The disappearance of neurons lacking the Ret-receptor in this brain area has now for the first time been observed in mice, since the scientists were able to eliminate the receptor specifically in neurons of this brain region. The mice thus altered are viable and live as long as their normal relatives. "For the first time it was now possible to study the effects of missing GDNF signals on the establishment and maintenance of the nigrostriatal pathway (a neural pathway connecting the substantia nigra with the striatum)", stated Rdiger Klein, Director at the Max Planck Institute of Neurobiology and head of the research team. Animals that lack GDNF and its receptor in all neurons are not viable and therefore it was not possible to investigate the precise role of GDNF and its receptor in the adult and aging brain.