Decades after the 1918 influenza pandemic, epidemiologists noted an uptick in the number of people with diminished mobility and other neurological symptoms reminiscent of Parkinson's disease. But despite this and other hints, the idea that viruses can trigger neurodegenerative disease has remained controversial. Now researchers report new evidence for such a link: Mice infected with the H5N1 avian influenza virus lose the same dopamine-releasing neurons that are destroyed by Parkinson's disease.
The new study was inspired in part by video footage of chickens, geese, and ducks collected in Laos by researchers working with the World Health Organization's surveillance program, says senior author Richard Smeyne, a developmental neurobiologist at St. Jude Children's Research Hospital in Memphis, Tennessee. "The birds looked like they had Parkinson's disease," Smeyne says. "They were tremoring, falling side to side, and having difficulty with movements." So far there have been no reports of Parkinson's disease in human survivors of the H5N1 flu, Smeyne says, but because only a few years have passed since the first cases were reported, it's too early to know whether those infected are at increased risk.
To learn more about the virus's effect on the nervous system, Smeyne and colleagues sprayed a solution containing the virus into the noses of 225 mice. All of the mice developed tremors and movement difficulties. Using an antibody that binds and labels a specific viral protein, the researchers tracked the virus as it first infected nerves in the gut 2 or 3 days after the nasal spray and then successively appeared in the brain stem and midbrain and ultimately infected much of the rest of the brain within 10 days. By 21 days, mice had cleared the virus. But at the end of the 90-day study, the brain regions that had been infected still exhibited signs of inflammation and had elevated levels of phosphorylated alpha-synuclein, the main ingredient in the abnormal clumps of protein that are a hallmark of Parkinson's and certain other neurodegenerative diseases, the researchers report online this week in the Proceedings of the National Academy of Sciences. The researchers also report that the number of dopamine-releasing neurons in the substantia nigra--the neurons that die off in Parkinson's disease--declined by 17% in the infected mice.
Smeyne notes that 17% is a small reduction compared with the 70% or so loss of dopamine neurons in people with full-blown Parkinson's disease. He suspects that H5N1 infection alone is insufficient to cause Parkinson's, but it may make the brain more susceptible, especially in combination with other factors, such as unlucky genetics, another environmental trigger, or simply old age.
"It's a very exciting paper," says Malú Tansey, a neuroscientist who studies inflammation and neurodegenerative disease at Emory University in Atlanta. Tansey says Smeyne's team has provided compelling evidence that the virus can sneak into the brain via the peripheral nervous system and that it plays a role in killing dopamine neurons. That said, she doesn't see the findings as cause for panic. "I don't think people should be overly concerned if they're exposed to avian flu virus that they're going to get Parkinson's disease," Tansey says. "But it should prompt [more] investigators to reexamine inflammation as a potential contributing factor to neurodegenerative disease."