“Friendly fire” by the body’s own immune system may damage a pathway at the base of the brain that is vital in the execution of smooth, coordinated movements.
This in turn could lead to symptoms associated with Parkinson-like diseases, according to University of Florida and Mayo Clinic Florida scientists.
Scientists have suspected that exposure to viruses and other environmental factors may trigger Parkinson-like symptoms, but it has remained a mystery as to why this exposure would actually destroy certain areas of the brain.
“In the movie ‘Awakenings,’ it was suggested that people who previously suffered from an infection like the flu developed Parkinsonism, probably because of degeneration in a brain pathway known as the nigrostriatal tract. But the links between infection and subsequent Parkinsonism have always been controversial,” said Dr. Todd Golde, director of the UF College of Medicine’s Center for Translational Research in Neurodegenerative Disease.
“Our data show that when a certain master protein that stimulates the immune system and antiviral response is expressed at high levels, it causes neuronal loss primarily in the nigrostriatal tract, thereby creating vulnerability to Parkinson’s and similar movement disorders.”
The symptoms in the disorders that are collectively called Parkinsonism are the result of degeneration and death of nerve connections that produce dopamine.
The most well-known Parkinsonism — Parkinson’s disease — affects more than 1 million Americans, causing individuals to gradually develop movement problems, including slowness, tremors and stiffness.
In the study, high levels of interferon gamma (the master protein which regulates immune system gene activity and coordinates immune defenses) resulted in widespread brain inflammation in model systems. However, most of the brain did not degenerate — only the nigrostriatal tract.
The results give scientists a clue as to why different areas of the brain seem more vulnerable to the ravages of different neurodegenerative diseases and offer a target to explore in the search for preventions and treatments for Parkinsonisms.
“Epidemiological studies and anecdotal observations aside, previous studies have never shown a direct link between chronic inflammation and Parkinson’s pathology,” said Paramita Chakrabarty, a postdoctoral fellow in Golde’s laboratory.
“We have shown that a small protein produced by our bodies in response to infections, called interferon-gamma, can directly lead to the loss of cells in the brain regions that are selectively targeted in Parkinson’s patients. More importantly, these changes were age-progressive, thus giving us an opportunity to initiate treatment in an early therapeutic window when the disease pathology is minimal.”
Researchers had originally set out to understand interferon gamma’s role in Alzheimer’s disease and dementia — conditions more associated with confusion and memory loss than movement problems.
“In general, we have had few clues as to why certain people are at risk for Parkinsonism, and this gives us an interesting possibility to explore,” said Golde, who is a professor in the department of neuroscience at UF’s McKnight Brain Institute.
“Namely, that infection or other factors that cause certain type of brain inflammation and high levels of interferon gamma can predispose one to Parkinsonism or even cause it outright.”
The study is published in Nature Neuroscience.
Source: University of Florida