A groundbreaking study conducted by researchers from Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, and Columbia University Vagelos College of Physicians and Surgeons has uncovered a surprising connection between SARS-CoV-2, the virus responsible for COVID-19, and dopamine neurones in the brain. The findings suggest a potential explanation for the neurological symptoms experienced by some long COVID patients, such as brain fog, depression, and lethargy.
The study, published in Cell Stem Cell on January 17, reveals that SARS-CoV-2 has the ability to infect dopamine neurones, which are responsible for producing dopamine, a neurotransmitter that plays a crucial role in various brain functions, including pleasure, motivation, memory, sleep, and movement. When these neurones become infected, they enter a state of senescence, losing their ability to function properly and triggering inflammation in the brain.
The research team initially set out to investigate how different cell types respond to SARS-CoV-2 infection. Using human stem cells, they generated various cell types and exposed them to the virus. Surprisingly, only dopamine neurones activated the senescence pathway upon infection, while other neuronal cell types remained unaffected.
The researchers discovered that approximately 5% of dopamine neurones could be infected by SARS-CoV-2, a relatively small percentage compared to lung cells, which are the virus’s primary target. However, even this small population of infected neurons can have a significant impact on brain function and contribute to the development of neurological symptoms.
To further understand the implications of SARS-CoV-2 infection on dopamine neurones, the team examined gene activity in infected neurones and compared it to autopsied dopamine neurones from COVID-19 patients. They found that the gene signatures were identical, including genes associated with inflammation. This suggests that the findings from lab-grown neurones accurately reflect what occurs in the brains of COVID-19 patients.
In an effort to protect dopamine neurones from infection and senescence, the researchers screened several FDA-approved drugs. Three drugs, namely riluzole (used to treat ALS or Lou Gehrig’s disease), metformin (used to treat diabetes), and imatinib (used to treat cancer), were identified as potential protectors against SARS-CoV-2 infection in dopamine neurones. Further research on these drugs may provide insights into preventing the virus’s impact on the brain.
While the clinical relevance of these findings is still uncertain, the researchers suggest that long COVID patients should be monitored for an increased risk of developing Parkinson’s disease-related symptoms. Senescence of dopamine neurons is a hallmark of Parkinson’s disease, and understanding the potential long-term effects of SARS-CoV-2 infection on these neurones could prove crucial in managing and treating long COVID.
It is important to note that not all individuals exposed to COVID-19 will experience neurological symptoms, as several factors, including disease severity and genetics, come into play. Ongoing human population studies are exploring these factors to gain a better understanding of the risk for neurological complications.
The implications of this study are far-reaching, offering new insights into the complex relationship between SARS-CoV-2 and the brain. By uncovering the link between the virus and dopamine neurones, researchers have taken a significant step towards understanding the neurological symptoms associated with long COVID. Continued research in this field may pave the way for innovative treatments and interventions to alleviate the long-term effects of COVID-19 on the brain.
