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Scripps Research Institute team identifies a potential cause of Parkinson's disease
Date:11/19/2012

cytokines investigated for their role as mediators of allergic reactions and for their anti-inflammatory action.

With further study, the researchers made the startling discovery that in the mouse brain, IL-13Ra1 is found only on the surface of dopaminergic neurons. "This was a 'Wow!' moment," said Brad Morrison, then a TSRI postdoctoral fellow and now at University of California, San Diego, who was first author of the paper with Cecilia Marcondes, a neuroimmunologist at TSRI.

Conti agrees: "I thought that these were very interesting coincidences. So we set out to see if we could find any biological significance."

The scientists didbut not in the way they were expecting.

'Something New Going On'

The scientists set up long-term experiments using a mouse model in which chronic peripheral inflammation causes both neuroinflammation and loss of dopaminergic neurons similar to that seen in Parkinson's disease. The team looked at mice having or lacking IL-13Ra1 and then compared the number of dopaminergic neurons in the brain region of interest.

The researchers expected that knocking out the IL-13 receptor would increase inflammation and cause neuronal loss to get even worse. Instead, neurons got better.

"We were very surprised at first," said Conti. "When we stopped to think, we got very excited because we understood that there was something new going on."

Given that cells fared better without the receptor, the team next explored whether damage occurred when dopaminergic neurons that express IL-13Rα1 were exposed to IL-13 or IL-4. But exposure to IL-13 or IL-4 alone did not induce damage.

However, when the scientists exposed the neurons to oxidative compounds, they found that both IL-13 and IL-4 greatly enhanced the cytotoxic effects of oxidative stress.

"This finally helps us understand a basic mechanism of the increased susceptibility and preferential loss of dopam
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Contact: Jann Coury
jcoury@scripps.edu
858-784-8245
Scripps Research Institute
Source:Eurekalert  

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