Previous studies had isolated H5N1 in the nervous system. But this is the first to show the path the virus takes to enter the brain as well as the aftermath of the infection. Smeyne said the virus' path from the stomach through the nervous system and into the brain is reminiscent of how Parkinson's unfolds.
In this study, mice were infected with an H5N1 flu strain isolated in 2004 from a patient in Vietnam. Robert Webster, Ph.D., said the strain remains the most virulent of the avian flu viruses. Webster, a co-author of the study, holds the Rose Marie Thomas Chair in Infectious Diseases at St. Jude.
About two-thirds of the mice developed flu symptoms, primarily weight loss. After three weeks there was no evidence of H5N1 in the nervous systems of the mice that survived.
But the inflammation the infection triggered within the brain continued for months. It was similar to inflammation associated with inherited forms of Parkinson's. Although the tremor and movement problems disappeared as flu symptoms eased, investigators reported that 60 days later mice had lost roughly 17 percent of dopamine-producing cells in SNpc, a structure found in the midbrain.
Researchers also found evidence that the avian flu infection led to over-production of a protein found in the brain cells of individuals with both Alzheimer's and Parkinson's diseases. The protein, alpha-synuclein, collected in H5N1-infected cells throughout the brain, including the midbrain where key dopamine-producing cells are located. There was little protein accumulation in the brain cells of uninfected mice.
The study marks the first time scientists were able to naturally trigger the protein build-up in an experimental Parkinson's system. "The virus activates this protein," Smeyne explained.
Other authors in this paper include Haeman Jang, David Boltz and Yun Jiao (St. Jude); and Katharine Sturm-Ramirez and Kennie Shephard (formerly of St. Jude).
This work was supported in part by the National Institute of Allergy and Infectious Diseases, National Parkinson's Foundation, Michael J. Fox Foundation, National Institutes of Health and ALSAC.
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