SARS-CoV-2 infection can increase the risk of brain degeneration seen in Parkinson's disease

SARS-CoV-2 infection can increase the risk of brain degeneration seen in Parkinson’s disease

Brain fog, headache, and insomnia are some of the neurological symptoms doctors have noticed in COVID-19 patients. The neurological consequences after a viral infection are not new – in fact, in the aftermath of the 1918 influenza pandemic, it took nearly a decade for sufferers of the neurological syndrome called “post-brain Parkinson’s” to emerge. But the mechanisms by which viruses affect the brain are not well understood. Now, Jefferson and his collaborators have shown in a new study in mice, that the SARS-CoV-2 virus responsible for the COVID-19 pandemic can increase the risk of brain degeneration seen in Parkinson’s disease.

Parkinson’s disease is a rare disease that affects 2% of the population over 55, so an increased risk is not necessarily a reason to panic. But understanding how the coronavirus affects the brain can help us prepare for the long-term consequences of this pandemic.”

Richard Smyne, PhD, director of the Jefferson Comprehensive Center for Parkinson’s Disease and Movement Disorder at the Vicki and Jack Farber Institute of Neuroscience and first author of the study

Search published in movement disorders on May 17yIt builds on previous evidence from Smeyne’s lab showing that viruses can make brain cells or neurons more susceptible to damage or death. In that previous study, researchers found that mice infected with the H1N1 influenza strain responsible for the 2009 influenza pandemic were more likely to have MPTP, a toxin known to induce some of the hallmarks of Parkinson’s disease: primarily the loss of neurons. Expression of the chemical dopamine and increased inflammation in the basal ganglia, a brain region essential for movement. The findings in mice were later confirmed in humans by researchers in Denmark, who showed that influenza nearly doubled the risk of developing Parkinson’s disease within 10 years after initial infection.

In the current study, the researchers used mice that had been genetically modified to express the human ACE-2 receptor, which the SARS-CoV-2 virus uses to reach cells in our airways. These mice were infected with SARS-CoV-2 and were allowed to recover. Importantly, the dose chosen in this study is consistent with moderate COVID-19 infection in humans, with approximately 80% of infected mice surviving. Thirty-eight days after the surviving animals recovered, one group was injected with a low dose of MPTP that usually causes no neuronal loss. The control group was given saline solution. Two weeks later, the animals were sacrificed and their brains examined.

The researchers found that COVID-19 infection alone had no effect on dopaminergic neurons in the basal ganglia. However, mice given a low dose of MPTP after recovering from infection showed the classic pattern of neuronal loss in Parkinson’s disease. This increased sensitivity after infection with COVID-19 was similar to what was seen in the influenza study; This suggests that both viruses could lead to an equivalent increase in the risk of developing Parkinson’s disease.

“We’re thinking about the ‘multiple hit’ hypothesis of Parkinson’s disease – the virus itself doesn’t kill the neurons, but makes them more susceptible to a ‘second hit’, such as a toxin, bacteria or even an underlying genetic mutation,” explains Dr. Smeyne.

Both influenza and SARS-CoV2 have been found to cause a “cellular storm,” or an increase in the production of inflammatory chemicals. These chemicals can cross the blood-brain barrier and activate the brain’s immune cells – microglia. In fact, the researchers found increased numbers of activated microglia in the basal ganglia of mice that had recovered from SARS-CoV2 and received MPTP. While the mechanism is not fully understood, researchers believe that the increased microglia inflames the basal ganglia and causes cellular stress. This then lowers the neuron’s threshold for subsequent stress tolerance.

This study was co-led by collaborator Peter Schmidt, PhD, a neuroscientist from New York University. “We were concerned about the long-term consequences of viral infection,” Dr. Schmidt said. “Dr. Smeyne is a pioneer in this field of research and Jefferson was the ideal location to perform the analysis.”

The researchers plan to determine if the vaccines can mitigate the experimental increase in Parkinson’s disease associated with a previous SARS-CoV-2 infection. They also test for different types of virus, as well as doses that correspond to milder cases in humans.

While their findings so far strengthen the potential link between the coronavirus and Parkinson’s disease, Dr. Smein says there are some important caveats. “First of all, this is preclinical work. It is too early to say whether we will see the same thing in humans, given that there appears to be a 5-10 year period between any changes in clinical manifestations of Parkinson’s disease in humans.” But he says this delay can be used to our advantage. “If it turns out that COVID-19 increases the risk of developing Parkinson’s disease, it will be a significant burden on our community and health care system. But we can anticipate this challenge by enhancing our knowledge of potential ‘second strikes’ and mitigation strategies.”


Thomas Jefferson University

Journal reference:

Smeyne, R. J., et al. (2022) COVID-19 infection enhances susceptibility to oxidative stress-induced Parkinson’s disease. movement disorders.

2022-05-19 01:38:00

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