SARS-CoV-2 can infect dopamine neurons causing senescence

A new study reported that SARS-CoV-2, the virus that causes COVID, can infect dopamine neurons in the brain and trigger senescence, when a cell loses the ability to grow and divide. Researchers from Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, and Vagelos College of Physicians and Surgeons at Columbia University suggest that further research into this finding could shed light on neurological symptoms associated with long COVID, such as brain fog, lethargy and depression. .

The results, published in Stem cell on January 17, show that dopamine neurons infected with SARS-CoV-2 stop working and send chemical signals that cause inflammation. Normally, these neurons produce dopamine, a neurotransmitter that plays a role in feelings of pleasure, motivation, memory, sleep and movement. Damage to these neurons is also linked to Parkinson’s disease.

“This project started by studying how different cell types in different organs respond to SARS-CoV-2 infection. We tested lung cells, heart cells, pancreatic beta cells, but the senescence pathway does not “is activated only in dopaminergic neurons,” the official said. author Dr. Shuibing Chen, director of the Center for Genomic Health, Kilts Family Professor of Surgery, and member of the Hartman Institute for Therapeutic Organ Regeneration at Weill Cornell Medicine. “It was a completely unexpected result.”

Determining the impact of SARS-CoV-2 on different cells

Previously, Dr. Chen led efforts to generate multiple cell types from human stem cells and test them to determine which ones could be infected by SARS-CoV-2. This allowed researchers to study the spectrum of tissues susceptible to infection during COVID, which presents a wide range of symptoms in different patients. They also studied autopsy samples from virus-infected patients to confirm their observations from lab-grown cells.

Surprisingly, they found that a small percentage of dopamine neurons exposed to SARS-CoV-2 were infected, around five percent. “The infection rate of dopamine neurons is not as high as that of lung cells, the main target of the virus, but even a small population of infected cells can potentially have a serious effect,” Dr. Chen said.

Interestingly, not all neuronal cell types were vulnerable to viral infection. The researchers observed that cortical neurons were not permissive to SARS-CoV-2 infection under identical experimental conditions.

Protect dopamine neurons

In this paper, researchers used transcriptional profiling to identify how SARS-CoV-2 infection altered gene activity and resulting changes in cell behavior. “We found that only dopamine cells had the senescence pathway activated,” Dr. Chen said. In contrast, senescence pathway genes were not significantly activated with SARS-CoV-2-infected lung organoids, pancreatic cells, liver organoids, or heart cells.

The researchers found that the genetic signatures – the unique pattern of gene activity – of infected dopamine neurons grown in the lab and dopamine neurons from COVID autopsy samples were the same. This included genes that triggered chemical signals of inflammation.

Next, they looked for ways to protect neurons to reduce the risk of neurological defects when a patient is infected with the virus.

The researchers tested drugs already on the market for various conditions to find one that either prevented SARS-CoV-2 infection or rescued infected dopamine neurons from senescence. The analysis identified three drugs that blocked SARS-CoV-2 infection, preventing senescence of dopamine cells: riluzole (treats ALS or Lou Gehrig’s disease), metformin (treats diabetes) and imatinib (treats cancer). Further studies of these drugs may find a way to prevent the virus from attacking the brain.

Although most people will be exposed to COVID, only some people will be affected, as many factors are involved in the risk of neurological symptoms, including disease severity and genetics. Human population studies explore this aspect further.

Although the clinical relevance of these findings is not yet clear, since senescence of dopamine neurons is a hallmark of Parkinson’s disease, the researchers suggest that patients with long COVID should be monitored for an increased risk of develop symptoms related to Parkinson’s disease. To date, symptoms of Parkinson’s disease have not been widely reported in population studies.