Researchers uncover possible link between avian flu and Parkinson's disease

13 Aug Researchers uncover possible link between avian flu and Parkinson's disease

Infection with the avian influenza virus might cause a predisposition to Parkinson’s disease, according to research published this week in the Proceedings of the National Academy of Sciences. The following article is adapted from a recent report in The Scientist.
Epidemiological studies done in the 1980s showed that survivors of the 1918 Spanish influenza, a flu pandemic that killed more than 50 million people worldwide, had a greater incidence of Parkinson’s disease later in life than the general population. Recent studies have suggested that the currently circulating strain of avian influenza has similar pathology to the 1918 flu. Though the subtypes of the viruses are different (Spanish flu shares the H1N1 subtype with the current H1N1 swine flu, whereas avian influenza has an H5N1 subtype), both viruses appear to enter the central nervous system (CNS) and can cause encephalitis, or inflammation of the brain.
The study did not look at the ability of the current H1N1, or swine flu strain, to infect the CNS.
Richard Smeyne at St. Jude’s Hospital in Memphis, Tennessee, and colleagues infected mice with avian flu and tracked how the infection progressed to the nervous system. “We thought [the virus] would get in [to the CNS] via the blood stream,” through the blood brain barrier, said Smeyne. Instead, the virus entered “in a backdoor way,” infecting the axon terminals of peripheral neurons first, specifically those of the gut and lung. The virus then traveled from the axon to the neuron cell body, where the researchers think it may be able to infect other neurons to eventually arrive in the brain.
Strikingly, said Smeyne, “this virus was mimicking the pattern of progression of Parkinson’s disease.” Some scientists think that Parkinson’s disease starts in peripheral neurons and slowly makes its way into the CNS, much like the progression of the flu infection. “It is interesting to me,” said Tansey, that the virus “clearly infects the areas that are the most sensitive to chronic inflammation,” such as the midbrain, where much of the neuronal death seen in Parkinson’s disease occurs.
Smeyne observed a loss of about 17% of dopamine-producing neurons in the infected mice. Parkinson’s patients normally lose between 50-80% of their dopamine-producing neurons, and the loss in Smeyne’s mice suggests a predisposition to the disease, he said. Although all traces of the virus were cleared from the brain after about 20 days, and there was no evidence of further neuron loss, the virus appeared to have caused a prolonged activation of microglial cells, the immune cells that mediate inflammation in the brain. That effect — observed 90 days post-infection — suggests that these cells had become much more sensitive to subsequent neural insults, said Smeyne.
The biggest risk factor for Parkinson’s disease, said Smeyne, is age. “We think what is happening with the influenza is that it’s shifting the curve” to speed the onset of the disease. Tansey cautioned, however, that the study doesn’t indicate the virus necessarily causes Parkinson’s, nor does it suggest that more common strains of influenza may predispose people to the disease.
It would be interesting to test whether the flu-infected mice would be more likely to develop full-blown Parkinson’s disease if they were allowed to age, she said, and to repeat the study in non-human primates.
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