A common virus has been used to trigger Parkinson’s-like brain damage and movement problems in mice, giving scientists a new way to study how viral infections may contribute to the disease.
Parkinson’s disease affects more than 10 million people worldwide and is the second most common neurodegenerative disorder after dementia. It is best known for its movement symptoms: tremors, stiffness, balance problems and slowed movement.
But at the cellular level, one of its defining features is the loss of dopamine-producing neurons in a part of the brain called the substantia nigra. What causes those neurons to die remains unclear, but viral infection has long been suspected as a potential contributor.
“The toxic-exposure models are useful for studying Parkinson’s, but not all people who are exposed to chemicals go on to develop Parkinson’s,” said study author Candice Brinkmeyer-Langford, a neurodegenerative disease expert at Texas A&M University.
That is the problem the new study set out to address. Most animal models of Parkinson’s rely on either genetic manipulation or the use of neurotoxins, which selectively destroy dopamine-producing neurons. These models are useful, but they do not necessarily reflect the more complex way Parkinson’s may develop in people, where ageing, genetics, environmental conditions, and immune responses are thought to play a role.
The researchers instead used Theiler’s murine encephalomyelitis, or TMEV, a naturally occurring pathogen in mice. TMEV has previously been used in models of neurological diseases such as multiple sclerosis (MS) and epilepsy, and earlier work had shown that it can infect dopamine-producing neurons in the substantia nigra. What had not been shown was whether that infection could produce the kind of lasting movement problems seen in Parkinson’s models.
To test this, the team injected TMEV into one side of the substantia nigra in adult male mice. Control mice underwent the same procedure but received only the carrier solution.
The researchers then tracked both brain changes and movement behavior for up to 20 weeks. One week after infection, the virus was detected inside a marker of dopamine-producing neurons at the injection site. By four weeks, those neurons had significantly degenerated on the infected side of the brain. Control mice didn’t show the same loss.
The brain damage also translated into movement problems. In a pole test, which measures coordination and movement speed, infected mice generally took longer to turn and climb down than controls. Their descent times were significantly worse at weeks four, 16 and 20, suggesting the deficit lasted well beyond the initial infection.
A gait analysis using a treadmill found a more subtle but still relevant change. Of 48 gait measurements analyzed, one measure related to how the left forepaw unloaded from the treadmill during walking was consistently reduced in infected mice and significantly different at 12 weeks. Because the virus was injected into the right side of the brain, which controls the left side of the body, that finding lined up with the expected pattern of one-sided motor impairment.
One of the more interesting details from the study is that the virus had been cleared out of the mice’s bodies by four weeks, but the dopamine neuron loss and movement problems persisted. That suggests the damage was not caused by an ongoing infection but by the lasting effects of the initial viral hit.
This does not mean a mouse virus causes Parkinson’s disease in humans. TMEV is a mouse-specific virus; the study was small, and the virus was injected directly into the brain, which is not exactly how viral infections usually announce themselves in everyday life.
But the study does provide a new model for investigating a serious possibility: that, in some circumstances, viral infection may trigger immune and inflammatory processes capable of damaging dopamine neurons.
The researchers say future work should compare the TMEV model with standard toxin-based Parkinson’s models, investigate early warning signs and biomarkers, and examine how the immune response to viral infection changes the brain.
“Viruses are known to cause entirely different diseases based on a person’s genetics,” Brinkmeyer-Langford said. “For example, the Epstein-Barr virus causes mononucleosis, but may also contribute to cancer or multiple sclerosis, and SARS-CoV-2 can attack the heart and brain as well as the lungs.”
The viral angle could matter because Parkinson’s is unlikely to have a single cause. For some people, genetics may dominate. For others, environmental exposures, inflammation or infection may help push an already vulnerable brain towards neurodegeneration.
For now, the study gives researchers a new tool: a way to model Parkinson’s-like brain damage that begins not with poisoning neurons, but with infection. And for a disease whose origins remain stubbornly shadowy, that may be a useful place to start.
The study was published in the journal Brain, Behavior, & Immunity – Health.
Source: Texas A&M University
Fact-checked by Mike McRae
