Uncontrolled neuronal death in the brain often gives rise to 
neurodegenerative illnesses like Parkinson or Alzheimer disease. Whether or 
not neurons have a long and healthy life is, apart from other factors, 
determined by the presence of neurotrophic factors. Scientists of the Max 
Planck Institute of Neurobiology have now provided unambiguous proof that the 
presence of the neurotrophic factor GDNF and its receptor Ret are essential 
for the survival of neurons in a specific brain region.  

   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 Rüdiger 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 
Rüdiger 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. 
 
"Surprisingly even without the Ret- receptor the nigrostriatal system 
developed normally", remarked Edgar Kramer, one of the leading scientists of 
the study. Only in adulthood the inability of these neurons to receive GDNF 
due to the missing receptor became evident and the older the animals grew, 
the more nerve cells died. 
 
Worldwide more than 100 million especially older people suffer from diseases 
of the brain that are characterized by a gradual loss of neurons. Depending 
on which region of the brain is affected the symptoms vary, e.g. Alzheimer 
patients suffer from a progressive loss of memory whereas in Parkinson 
disease failures of the motor system are most evident. However, the 
characteristic muscle shaking and the inability to initiate movement of 
Parkinson’s disease, from which also prominent people like Muhammed Ali and 
Michael J. Fox suffer, only become apparent after more than 50 percent of the 
neurons have died. 
 
"Our results will help us to understand which factors nerve cells fated to die 
in Parkinson’s patients need to survive" Rüdiger Klein stated. The published 
results are therefore of importance for promoting therapeutic approaches 
against Parkinson’s disease. 
 
Citation: Edgar R. Kramer, Liviu Aron, Geert M.J. Ramakers, Sabine Seitz, 
Xiaoxi Zhuang, Klaus Beyer, Marten P. Schmidt & Rüdiger Klein, Absence of Ret 
signaling in mice causes progressive and late degeneration of the 
Nigrostriatal system, PLOS Biology 2007, March 5, 2007 
 
Source: Max Planck Institute of Neurobiology

----------------------------------------------------------------------
To sign-off Parkinsn send a message to: mailto:[log in to unmask]
In the body of the message put: signoff parkinsn