summary: A new study reveals that SARS-CoV-2 can infect dopamine neurons, which may be associated with long-term coronavirus symptoms such as brain fog and depression. Studies have shown that these neurons enter a senescent state, stop functioning and cause inflammation. This finding was unexpected, as the study originally aimed to understand how different cell types respond to the virus, but this unique pathway was only discovered in dopamine neurons. .
Important facts:
- Approximately 5% of dopamine neurons can be infected by SARS-CoV-2, causing aging and inflammation, which may contribute to neurological symptoms in long-term COVID-19 infections.
- The study used human stem cells to generate different cell types and found that only dopamine neurons activate aging pathways upon infection.
- Three drugs, riluzole, metformin, and imatinib, were identified as potential protective agents against SARS-CoV-2 infection in dopamine neurons.
sauce: Weill Cornell University
A new study reports that SARS-CoV-2, the virus that causes the novel coronavirus, can infect dopamine neurons in the brain, causing aging in which cells lose their ability to grow and divide.
Researchers at Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, and Columbia University College of Physicians and Surgeons hope that further study of this finding could lead to long-term effects of the new coronavirus, including brain fog, lethargy, and depression. This suggests that related neurological symptoms may be elucidated.
The survey results are cell stem cells On January 17, researchers showed that dopamine neurons infected with SARS-CoV-2 stop functioning and send out 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 implicated in Parkinson’s disease.
“This project began to investigate how different cell types in different organs respond to SARS-CoV-2 infection. We examined the cells, and only the dopamine neurons were activated in the aging pathway,” said lead author Dr. Shuibing Chen, director of the Center for Genome Health and member of the Kilz Family Professor of Surgery. Weill Cornell Medicine’s Hartmann Institute for Therapeutic Organ Regeneration. “This was a completely unexpected result.”
Understanding how SARS-CoV-2 affects different cells
Previously, Dr. Chen led an effort to generate multiple cell types from human stem cells and test them to see which cell types SARS-CoV-2 infects. This allowed the researchers to investigate the range of tissues that can be infected during COVID-19, which causes different symptoms in different patients. They also studied autopsy samples from patients infected with the virus and confirmed their observations from cells grown in the lab.
Surprisingly, they found that a small percentage of dopamine neurons exposed to SARS-CoV-2, about 5 percent, were infected. “Although the infection rate of dopamine neurons is not as high as that of lung cells, which are the main target of the virus, even a small population of infected cells can have serious effects,” Dr. Chen said.
Interestingly, not all neuronal cell types are vulnerable to viral infection. The researchers observed that cortical neurons were not permissive to SARS-CoV-2 infection under identical experimental conditions.
Protection of dopamine neurons
In this paper, researchers used transcriptional profiling to determine how SARS-CoV-2 infection changes gene activity and, as a result, changes in cell behavior. “We found that only dopamine cells activate the aging pathway,” Dr. Chen said. In stark contrast, genes in the aging pathway were not significantly activated in lung organoids, pancreatic cells, liver organoids, or heart cells infected with SARS-CoV-2.
Researchers found that the gene signatures (distinctive patterns of gene activity) from infected lab-grown dopamine neurons and dopamine neurons obtained from autopsy samples of the new coronavirus were the same. This included genes that trigger chemical signals of inflammation.
They then looked for ways to protect neurons to reduce the risk of neurological defects if patients were infected with the virus.
Researchers tested already commercially available drugs for a variety of conditions to find drugs that prevent SARS-CoV-2 infection or rescue infected dopamine neurons from aging.
This screen identified three drugs that block SARS-CoV-2 infection and prevent dopamine cell aging: riluzole (treats ALS or Lou Gehrig’s disease), metformin (treats diabetes), and imatinib (treats diabetes). treatment). Further research into these drugs may lead to ways to prevent the virus from attacking the brain.
Although most people have been exposed to the coronavirus, only certain people are affected because the risk of neurological symptoms depends on many factors, including disease severity and genetics. Human population studies are further investigating this aspect.
Although the clinical relevance of these findings is not yet clear, the aging of dopamine neurons is a hallmark of Parkinson’s disease, so the researchers believe that patients with long-term COVID-19 infection may be at risk of developing Parkinson’s disease-related symptoms. suggests the need to monitor the increase in To date, symptoms of Parkinson’s disease have not been frequently reported in population studies.
This study was a collaboration with Dr. Lorenz Studer, director of the Center for Stem Cell Biology at Memorial Sloan Kettering Cancer Center. David D. Ho, Ph.D., Clyde ’56, Helen Wu, Professor of Medicine, Columbia University College of Physicians and Surgeons; Dr. Robert Schwartz is an associate professor in the Department of Gastroenterology and Hepatology, a member of the Sandra Edward Meyer Cancer Center at Weill Cornell Medicine, and a member of the NewYork-Presbyterian/Weill Cornell Medical Center. He is also a hepatologist at the center.
About this neurology and new coronavirus infection research news
author: Barbara Prempe
sauce: Weill Cornell University
contact: Barbara Prempeh – Weill Cornell University
image: Image credit is Liuliu Yang
Original research: Open access.
“SARS-CoV-2 infection causes aging of dopaminergic neurons” by Shuibing Chen et al. cell stem cells
abstract
SARS-CoV-2 infection causes aging of dopaminergic neurons
highlight
- hPSC-derived DA neurons are susceptible to SARS-CoV-2 infection
- SARS-CoV-2 infection of DA neurons triggers a cellular senescence response
- Several FDA-approved drugs have been identified to rescue aging DA neurons
- Cellular senescence was discovered in the substantia nigra tissue of patients infected with the new coronavirus.
summary
COVID-19 patients commonly exhibit signs of central and/or peripheral nervous system dysfunction. Here we show that human pluripotent stem cell (hPSC)-derived midbrain dopamine (DA) neurons are selectively susceptible and tolerant to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. .
SARS-CoV-2 infection of DA neurons triggers inflammatory and cellular senescence responses. High-throughput screening of hPSC-derived DA neurons identified several FDA-approved drugs that can rescue cellular senescence phenotypes by preventing SARS-CoV-2 infection.
We also identified inflammatory and cellular senescence features and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue from patients with COVID-19 infection. Additionally, we observed decreased numbers of neuromelanin+ and tyrosine hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients.
Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify potential neuroprotective agents for COVID-19 patients, and improve the neurology of COVID-19 patients. This suggests the need for careful long-term monitoring of these issues.