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-13Rá1 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 dopaminergic neurons to oxidative stress associated with neuroinflammation,” said Marcondes.
And, though not definitive, other studies have suggested that Parkinson’s disease might be more common among allergy sufferers. Since IL-13 plays a role in controlling allergic inflammation, Conti wonders if the IL-13 receptor system might explain this correlation.
If further research confirms the IL-13 receptor acts in a similar way in human dopaminergic neurons as in mice, the discovery could pave the way to addressing the underlying cause of Parkinson’s disease. Researchers might, for instance, find that drugs that block IL-13 receptors are useful in preventing loss of dopaminergic cells during neuroinflammation. And, since the IL-13 receptor forms a complex with the IL-4 receptor alpha, this might also be a target of interest. With much exciting research ahead, Conti said, “This is just the beginning.”
This research was funded by the Ellison Medical Foundation; National Institutes of Health grants AG028040 and DA030908; and the Ministry of Education, Culture, Sports, Science and Technology of Japan.
In addition to Morrison, Marcondes and Conti, the other authors on the paper, “IL-13Rá1 expression in dopaminergic neurons contributes to their oxidative stress-mediated loss following chronic systemic treatment with LPS,” were Daniel Nomura, Manuel Sanchez-Alavez, Alejandro Sanchez-Gonzalez, Indrek Saar, and Tamas Bartfai, from TSRI, Kwang-Soo Kim from Harvard University, Pamela Maher from the Salk Research Institute, and Shuei Sugama from the Nippon Medical School in Tokyo.About The Scripps Research Institute
Jann Coury | EurekAlert!
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