The 'tentacles' of SARS-Cov-2 are elongated. The infection, as we have verified during the pandemic, is capable of affecting multiple organs and systems of our body, causing a long list of problems.
In the brain, the particular imprint of Covid is singular, as has just been demonstrated by research from the Queensland Brain Institute in Brisbane (Australia) in which the Spanish Ramón Martínez-Mármol has participated.
According to their data, Covid-19 can cause neurons to fuse, which causes them to malfunction and can lead to neurological symptoms.. Although the studies have so far been carried out only in the laboratory, the researchers point out that the phenomenon could be behind some of the symptoms of persistent Covid, such as brain fog.. Details of the work are published in the journal Science Advances.
“Our results present a neural alteration that can persist for a long time in our brains,” says Martínez-Mármol via email. “We rule out that this is responsible for all the symptoms observed in patients with persistent Covid, but it may be a mechanism involved in some of them.”
The Spanish researcher Ramón Martínez-Mármol.
The ability of SARS-Cov-2 to cause some cells to fuse was known. For example, its effects on lung cells have been studied and several studies have pointed to fusion as one of the causes of the respiratory symptoms, sometimes very severe, caused by the infection.. However, until now its ability to cause a fusion between neurons had not been demonstrated.
In fact, “the neuronal fusion induced after a viral infection had not been demonstrated to date”, emphasizes Martínez-Mármol. This phenomenon, he explains, “had only been observed on a few exceptional occasions in certain invertebrates, such as the nematode Caenoarbditis elegans.”
The 'key' to the virus
According to experiments in mouse cell cultures and human brain organoids grown using stem cells, SARS-CoV-2 infection can cause fusion between neurons (and between neurons and other brain cells) through the ACE2 receptor, the 'key ' that the virus uses to penetrate those cells. In an already infected cell, the S protein of the virus uses other ACE2 receptors to trigger fusion with 'neighboring' neurons, as a way to continue expanding.
The fusion that the researchers were able to observe through staining of two different types of neurons in mouse and human brain organoids caused a disruption in communication between neurons.
Fused neurons present “a profound alteration in their pattern of electrical activity,” explains Martínez-Mármol. “By merging, they become fully synchronized activity, as if they were a single entity. And this can be a problem”, points out the Spanish researcher. Because precisely the “individuality” of neurons is a crucial factor for the functioning of the nervous system.
A disturbance in the 'electrical circuit'
The Australian team uses an analogy to explain the alterations caused by neuronal fusion. If we think about the electrical circuit that connects our house, the fusion would cause that, when a single switch is activated, either the lights in the kitchen and the bathroom would turn on at the same time or that they would all remain off.
“In 10% of cases, when neurons fuse with non-neuronal cells, such as astrocytes, the neurons stop working. This is significant since in our brain there are more non-neuronal cells than neurons”, adds the researcher, who stresses that it was precisely the Spaniard Santiago Ramón y Cajal who, at the end of the 19th century, established the Neuronal Theory and “postulated that neurons are units individuals that communicate with each other directionally through the space between them. This theory has been demonstrated in the vast majority of living organisms.. And we have now discovered that it can be precisely viruses that, after infecting neurons, have the capacity to alter said individuality”, explains Martínez-Mármol.
According to the researcher, the next steps that the team wants to take include studying the long-term effects of the aforementioned fusion in the brain of mice and analyzing how this fusion affects their behavior, memory or relationship with other animals.. They also want to extend the research to many other viruses, also fusogenic and that cause brain infections, to see if the effects on neurons are similar and if this fusion is the mechanism that explains the neurological symptoms that are sometimes associated with these disorders.. On the other hand, the team also wants to demonstrate the existence of fusion in brain samples donated to science, as well as evaluate possible treatments to “first prevent and then reverse said neuronal fusion”, concludes the researcher.