microglia – BioQuakes

Has anyone ever tried to talk to you the second after you woke up? It’s almost impossible to comprehend what they’re saying within those first ten seconds that you’re awake, right? Now imagine if those ten seconds lasted weeks, months, or even years, and you’ll be imagining the life of someone with post-COVID-19 brain fog.

“Brain fog,” is a feeling of confusion, inability to concentrate, fatigue, and overall “cloudy” mindedness that is a common residual symptom of the SARS-CoV-2 virus, affecting about forty percent of people who experience “long COVID” symptoms. Although unable to be detected through any sort of medical examination or test, post-COVID brain fog can have an overwhelming presence, causing people to be unable to work and frequently lasting for over a year. However, because brain fog only became an extremely common complaint of patients since the COVID-19 pandemic started, scientists know very little about the symptom.

In an attempt to discover more, scientists at Karolinska Institute, led by Carl Sellgren, researched how the SARS-CoV-2 virus affects the brain by infecting organoid brain cells with SARS-CoV-2. The experiment revealed that the virus caused neuron synapses to be destroyed at an unnaturally high rate. As we learned in AP Biology, neurons are signaling cells that exist throughout the body but make up most of the brain. Neurons are not actually connected- a small gap, called a synapse, between the end of one neuron (or the presynaptic membrane) and the start of the next (called the postsynaptic membrane) separates the two cells. Neurons signal each other by sending small particles called neurotransmitters across the synapse and into the next cell. Another common brain cell is microglia, which are immune system cells that dispose of dead cells and repair synapses. Microglia also destroy synapses, or connections between neurons, when they are no longer needed.

Sellgren’s study revealed that SARS-CoV-2 causes microglia in the brain to amplify the rate at which they destroy synapses, preventing many neurons from being able to make connections with other neurons. Assuming that a full human brain would respond the same way as brain organoids, this discovery explains why long-COVID patients with brain fog experience difficulty thinking. Amplified microglia activity is also associated with aging, which further supports the results of Sellgren’s experiment because people oftentimes become more forgetful with age.

With this new discovery to open the gates to more knowledge, scientists can begin to understand post-COVID brain fog more deeply and potentially hope for treatment for this symptom that affects the lives of thousands of people.

Recently, Massachusetts General Hospital (MGH) investigators have used a new sequencing method to identify a group of genes used by the brain’s immune cells, called microglia, to sense pathogenic organisms (bacteria that cause bacterial infection), toxins or damaged cells. Identifying these genes could lead to better understanding of the role of microglia both in normal brains and in neurodegenerative (nervous system) disorders. This discovery could also lead to ways to protect against brain dysfunctions caused by conditions like Alzheimer’s and Parkinson’s diseases.

The set of genes microglial have also been able to react with their environment. “We’ve been able to define, for the first time, a set of genes microglia use to sense their environment, which we are calling the microglial sensome,” says Joseph El Khoury, MD, of the “MGH Center for Immunology and Inflammatory Diseases and Division of Infectious Diseases, senior author of the study”. A type of macrophage microglia are known to consistently test their environment in order to sense any indication of infection, inflammation, and injured or dying cells. Depending on the situation they are involved in, the microglia reacts in a neurotoxic response, replying in a defensive protective manner. The microglia can “engulf pathogenic organisms, toxins or damaged cells or release toxic substances that directly destroy microbes or infected brain cells”. In this way microglia is extremely beneficial to the brain because it is able to identify infections before they have any direct contact with the brain. However, this neurotoxic response can also damage healthy cells and can “contribute to the damage caused by several neurodegenerative disorders”, so keeping the response under control is crucial.

El Khoury’s team’s “next step is to see what happens under pathologic conditions” and to define the sensome of microglia and other brain cells in humans, identifying how the sensome changes in central nervous system disorders, and eventually finding ways to safely manipulate the sensome. Discovering the microglia gene is a large and successful step to eventually finding a cure for infectious brain diseases, such as Alzheimer’s and Parkinson ’s disease.

BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: microglia

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