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Nerve cells regenerate brain 

Wednesday, 03 June 2009 
Garvan Institute 


New findings throw light on how the brain heals itself and may change the way 
we think about treating chronic neurodegenerative diseases like Parkinson's 
and Alzheimer's. 
Neuroscientists at Sydney's Garvan Institute of Medical Research have shown 
that nerve cells in the brain produce an anti-inflammatory molecule that 
allows the brain to repair itself. 
These findings, by Drs Bryce Vissel and Andrea Abdipranoto, are published 
online today in the international journal Stem Cells. 
Discovery of the brain's capacity to regenerate is very recent. Neural stem 
cells were first discovered in the brain in the early 1990s, but it took 
scientists a further 10 years to show that they can regenerate nerve cells in 
the brain.
 
"Given that we now know regeneration can occur, we want to understand what 
drives it and what blocks it, particularly in diseases like Parkinson's and 
Alzheimer's." said Dr Vissel. 
"We triggered rapid neurodegeneration in the brains of mice, and it was 
immediately followed by a very rapid regenerative response. We wanted to know 
why this response could occur so effectively after acute neurodegeneration. 
"On further investigation, we found high levels of a molecule known as Activin 
A whenever regeneration occurred. This was especially interesting because 
Activin A is released from nerve cells. 
"Clearly Activin A was playing an important part in the regenerative process, 
so we triggered neurodegeneration and at the same time blocked Activin A. The 
difference was dramatic. Regeneration all but ground to a halt." 
"After these initial experiments, we thought that nerve cells may directly 
drive regeneration by releasing Activin A. We came to realise, however, that 
the main action of Activin A was to block inflammation in the brain after 
neurodegeneration or injury." 
"We confirmed this by introducing another anti-inflammatory molecule, while 
continuing to block Activin A. As anticipated, the substituted anti-
inflammatory allowed regeneration to occur." 
"Inflammation is the body's way of trying to clear up a mess. We've shown 
that, if uncontrolled, it seems to be the very thing that can prevent 
regeneration and prevent healing of the brain." 
Having done this study in a model of acute degeneration, the group is now 
doing the same work in chronic degenerative models. 
It is likely that inflammation aggravates existing damage in the central 
nervous system of people with Parkinson's, Alzheimer's and motor neuron 
disease. Vissel and colleagues believe that chronic inflammation is probably 
providing a harmful feedback loop, preventing regeneration and contributing to 
progressive decline. 
"Clearly the brain's anti-inflammatory response is not working well in chronic 
neurodegenerative diseases," said Vissel. 
"There are a number of studies showing that people who take non-steroidal 
anti-inflammatory drugs have a lower risk of Alzheimer's and Parkinson's 
disease." 
Should the group confirm that inflammation is blocking regeneration in 
Parkinson's, Alzheimer's and motor neuron disease, Activin A and derivatives 
need to be investigated as potential therapeutics. 


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