Avoiding Post-COVID ‘Brain Fog’

Memory loss and difficulty learning are two of the numerous symptoms observed in patients with COVID-19. However, little is understood about the processes behind cognitive deficits like these, popularly known as brain fog.

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Blood vessel endothelial cells (green) and basement membrane (red) in the brain. Image Credit: Sarah Lutz

In a new study, researchers from the University of Illinois Chicago discovered a mechanism that causes neurological issues in mice infected with SARS-CoV-2, the virus that causes COVID-19. The researchers also discovered a therapy that prevented these alterations. Sarah Lutz, an assistant professor of anatomy and cell biology at the College of Medicine, led the study, which was published in the journal Brain.

The study focused on the blood-brain barrier, which is involved in various neurological diseases such as multiple sclerosis. Normally, this barrier shields the brain from potentially hazardous cells or substances in the circulation. Researchers discovered that infected mice had leaky blood-brain barrier vessels and poor memory or learning.

To figure out why, the researchers examined blood vessels from infected mice's brains to identify which genes had the largest changes. They discovered a substantial drop in Wnt/beta-catenin, a signaling system that maintains the blood-brain barrier and protects the brain from injury.

Based on these findings, the researchers investigated whether a gene treatment that promotes the Wnt/beta-catenin pathway could prevent brain damage in SARS-CoV-2-infected mice.

The treatment accomplished just that.

They had less blood-brain barrier leakage and less immune cell infiltration of the brain, which led to improvements in learning and memory.

Sarah Lutz, Assistant Professor, College of Medicine, University of Illinois Chicago

The scientists concentrated their investigation on older mice since, in individuals with COVID-19, age is a risk factor for cognitive impairment. They monitored the mice’s mild infections in particular. Thanks to vaccination, most COVID-19 cases are caused by mild infections rather than serious ones. Still, Lutz said, even mild infections can affect cognitive impairment.

Although developing a treatment to stop post-infection cognitive deficits in humans is still a long way off, this study is a significant step in the right direction, according to Lutz.

She added, “Anytime you can identify a molecular mechanism that contributes to a disease, you’re learning about basic biology and what causes disease in general. This research suggests that improving blood-brain barrier integrity could have benefits in preventing complications of COVID-19.

Dr. Jalees Rehman, a co-author of the study and the Benjamin Goldberg Professor and head of the UIC Department of Biochemistry and Molecular Genetics, highlighted that one important lesson from the COVID-19 pandemic is that even minor infections can have a tremendous effect on organs, including the brain.

There is a need for more research on respiratory infections that can affect the brain. The good news is that by studying the molecular signals activated by the infection as well as during the subsequent inflammation when the immune system responds to infection, one can develop new targeted therapies which prevent further damage to the brain and other organs.”

Dr. Jalees Rehman, Study Co-Author and Benjamin Goldberg Professor, University of Illinois Chicago

Troy Trevino, Avital Fogel, Guliz Otkiran, Seshadri Niladhuri, Mark Sanborn, Jacob Class, Ali Almousawi and Justin Richner are the other UIC authors.

Source:
Journal reference:

Trevino, T. N., et al. (2023). Engineered Wnt7a ligands rescue blood–brain barrier and cognitive deficits in a COVID-19 mouse model. Brain. doi.org/10.1093/brain/awae031

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