Why does COVID-19 cause brain fog? Scientists may finally have an answer.

Scientists at the Karolinska Institutet in Sweden infected brain organoids (lab-grown brain tissue about the size of a pinhead) with the virus that causes COVID. Accelerate connection destruction between neurons called synapses.

This discovery enhances our understanding of how it grows SARS-CoV-2 Enters Central Nervous System and Causes DiseaseIn the last two years scientists have Long-standing neurological and behavioral problems in COVID-19 patientsOne such condition, known as brain fog, causes disorientation, memory loss, chronic headaches, and numbness and affects most people. 40% of long-term COVID patients.

Psychiatrist and cell biologist Karl Sellgren and his team at the Karolinska Institutet are using organoids to understand the effects of SARS-CoV-2 on the brain and whether it can help explain neurological symptoms. I decided to find out.

Their study concludes that too much disruption of connections between neurons and excessive pruning may be causing long-lasting brain fog in COVID patients. Samudyata, a postdoctoral fellow at the Karolinska Institutet who led the study and goes by one name, said:

Neuroscientist Ana Osorio Oliveira, co-author of Sergren’s lab, said, “It was very impressive that such a small amount of virus could spread so quickly into the organoids and eliminate an excessive number of synapses.” said.A study was published in a journal molecular psychiatry.

“This study fits well with ours and several others,” says Madeline Lancaster, a neurobiologist at the MRC Molecular Biology Laboratory in Cambridge, UK.Using brain organoids, the Lancaster study Reveals that SARS-CoV-2 damages the brain’s protective barrierWhen this barrier is breached, pathogens, abnormal immune cells, and inflammatory compounds can enter the cerebrospinal fluid and brain.

Pruning connections between neurons is essential for learning

The brain consists of a dense and dynamic network of neurons that communicate through synapses that change as humans learn. “A synapse is essentially how cells talk to each other, how information is passed from one part of the brain to another,” says Lancaster.

Synapses are responsible for all the brain’s functions, from memory to movement control to how we feel emotions, and they’re constantly being rebuilt. “That’s how we learn,” she says.

Junctions between neurons that frequently talk to each other have knobby terminals that produce neurotransmitters (chemicals that transmit signals to other neurons) that travel across the interneuronal gap known as the synaptic cleft. increase. Conversely, neurons with less or no communication are removed or pruned by immune cells called microglia, resulting in fewer synapses. microglia It makes up up to 17% of some cell populations in the human brain and plays a housekeeping role. Feeds on dead cells and travels through the brain, cleaning weak synapses.

nevertheless Synaptic pruning is most active in brain development In fetuses and infants, it continues throughout life in a healthy brain, Needed to encode new memories and erase what the brain no longer needsSynaptic pruning is also important brain recovering from injury; strengthen synapses as lost skills are re-learned, removing those that no longer work.

Studying Nerve Injury Using Brain Organoids

Studying the direct relationship between COVID-19 and cognitive impairment such as brain fog is difficult in the living brain. As such, research is often limited to the cadavers of her COVID-19 patients. But brain organoids, called minibrains, allow scientists to see in real time how SARS-CoV-2 affects living tissue.

Using brain organoids, Oliveira and her colleagues found that the virus itself was activating microglia rather than directly pruning synaptic connections.

“After being infected with SARS-CoV-2, we somehow found that microglia became immunoreactive and ate more synapses than normal,” says Samudyata.

The study is important because it clearly demonstrates quantitative differences in microglial activity and its impact on synapses after COVID-19, says Ayush Batra, a neurologist at Northwestern University Feinberg School of Medicine. increase.

However, too much synaptic pruning can be detrimental, neurodevelopmental disorders like that schizophreniaeven as neurodegenerative disease such as Alzheimer’s disease and Parkinson’s disease.

Excessive synaptic clearing that occurs in brain organoids after SARS-CoV-2 infection, if it also occurs in humans, disrupts critical connections and explains why some with COVID-19 suffer long-term neurological symptoms It may be possible.

“Too much synaptic clearing is expected to affect the ability to form new memories and retain existing ones, and may help explain the slowing of brain function seen in brain fog.” There is,” says Lancaster.

This is consistent with research conducted at the US National Institutes of Health. Antibodies produced in response to SARS-CoV-2 can attack cells lining blood vessels in the brainEven if the virus does not enter the brain directly, it activates microglia causing damage and inflammation.As Batra’s team has shown, some COVID patients not sick enough to be hospitalized continue to experience neurological symptoms after more than a year early infection.

Does Synaptic Loss Cause Brain Shrinkage?

a British studies also showed Even mild COVID-19 can shrink the brain through loss of gray matter (the outermost layer of the brain that is made up of cell bodies and essential for movement, memory and emotional regulation).It causes physical changes equivalent to 10 years of aging. Gwenael Duhaut, a neuroscientist at the University of Oxford who led the study, said, “In general, we still don’t know what contributes to the reduction in gray matter mass and thickness observed on MRI. hm,” he said.

Douaud says synaptic depletion may account for a small percentage of gray matter changes, as shown in Samudyata’s study, but to identify other factors that lead to brain shrinkage, More studies combining imaging and tissue sectioning are needed.

Hyperactive microglia can cause problems in other ways. The current study also shows that the pattern of genes turned on/off by microglia in brain organoids after SARS-CoV-2 infection mimicked gene activity seen in neurodegenerative diseases.This may explain why there is 3x higher risk of developing a neurological or psychiatric disorder Compared to people who were not infected with COVID-19 within 6 months. Adults over the age of 65 have little risk of developing dementia after being infected with COVID-19. Twice as many other respiratory infections.

But scientists warn that more research is needed to understand the effects of SARS-CoV-2 infection on the brain. Organoids resemble immature cells, such as in the fetal or postnatal state, which limits the extrapolation of results to mature adult brain cells.

“While these data are exciting and indicate a role for pro-inflammatory microglia in the underlying disease mechanisms of long COVID, much more is needed to validate these findings and build on them. We need research,” said Oliver Harschnitz, a group leader at Human’s Center for Neurogenomics Research. Technopol Institute in Milan, Italy.

We also don’t know if long-term COVID has irreversible effects on the brain. So as the pace of holiday and indoor winter activities picks up, Samudyata recommends taking precautions and staying up to date on vaccinations to minimize the chances of getting COVID again and again. advises Mr. It is not clear how the virus affects the brain in a detrimental way, but it is clear that it causes damage.