Brain Protecting-Cells May Improve Treatment of Cognitive Decline, HIV

Beneficial cells that protect against disease may not originate from immune system.

Investigators have long thought that certain immune cells protect the brain against disease and harmful pathogens. In a new study published by eLife, the authors discovered that these beneficial cells do not originate from the immune system, but are likely from the lining of the circulatory system.

These findings have widespread applications for understanding normal cognitive decline and how HIV infiltrates brain cells.

The blood-brain barrier is a layer of cells that line the brain’s blood vessels. The inner lining of blood vessels is called the endothelium, which is present throughout the body. Specifically, within the brain, the endothelial cells and nearby cells prevent toxins and microbes from infecting the brain.

A special population of cells covering the blood vessels on the surface of the brain is thought to be protective, but their function is not completely known, according to the study. The sentry cells destroy toxins, cellular waste, and microbes, which are then packaged into vesicles. The cells, called fluorescent granular perithelial cells (FGPs), give off a yellow glow when exposed to light.

In the new study, the authors discovered that FGPs are found on the surface of zebrafish brains, much like humans; however, the blood vessel-associated cells are not produced by the immune system, but by endothelial cells, according to the study.

FGPs are believed to play a significant role in brain conditions, and could be a potential entry point for HIV to infect brain cells. Additionally, age-related cognitive decline has been linked to lessened function of these sentry cells.

“Learning more about how FGPs function may lead to a greater understanding of dementia and other conditions,” said the study’s senior author, Brant Weinstein, PhD, of National Institute of Child Health and Development’s Section on Vertebrate Organogenesis.

The authors studied zebrafish to understand how different systems develop. Since embryonic zebrafish are transparent, researchers are able to watch their circulatory system develop.

In the study, the authors inserted a gene that marks cells that line the endothelium of veins and lymphatic system green to track their movement. Unsurprisingly, the fish’s lymphatic cells turned green, but there were also green cells covering the brains of the fish, according to the study.

When looking closely, the authors were able to identify the green cells in the brain as FGPs. Originally, the authors mistook FGPs to be macrophages, but upon analysis, they were discovered to be endothelial cells in the lymphatic system. The green marker allowed the authors to confidently say that the FGPs originated from endothelial cells in zebrafish.

In other experiments, the authors inserted a green fluorescent protein into the tissues that create blood and lymph vessels in embryonic zebrafish. The authors were able to image FGPs being developed from the endothelium, according to the study. When the fish matured, green FGPs covered the fish’s brains, which confirmed the cells’ origin.

The study authors plan to continue their studies of how FGPs play a role in blood vessels and the blood-brain barrier. Since developing zebrafish can be observed under a microscope, the animals are crucial to exploring the role of FGPs in protecting the brain, the study concluded.