Thanks to more than a century of modern neuroscience, we have made significant strides in understanding the brain. However, we have only just begun to understand how this surprisingly complex organ works.
Deepening into this mysterious puzzle, researchers from the Faculty of Pharmaceutical Sciences at the University of Kyushu analyzed in unprecedented detail the development and genetic profile of a set of cells that make up the brain’s immune system.
Their new ideas published in a journal Naturecan pave the way for a better understanding of the origins and mechanisms behind leading brain pathologies such as Alzheimer’s disease and multiple sclerosis.
“Many people are familiar with how neurons connect together to send signals through the brain, but there are also blood vessels that supply the brain with oxygen and glial cells that act as a support network for the brain and the immune system,” said Takahira Masuda. led the study. “In fact, even the most generous estimates show that only about half of our brain cells are neurons, so studying other cells is just as important to discover how the brain works.”
With this in mind, the research team focused on a number of cells called “macrophages associated with the central nervous system,” a type of immune cell that protects the brain from infection. It is believed that these macrophages are involved in almost all known neurodegenerative diseases because of their critical role as brain immune cells.
Over the years, research has shown that there are many different types of these cells. For this study, the team was particularly interested in macrophages surrounding blood vessels and those located in the meninges – the layers surrounding the brain – known as “perivascular macrophages” and “meningeal macrophages”, respectively.
“So far, these cells have not been different from other immune cells, and how and where these critical cells develop has been much less studied,” Masuda continues. “Thus, we explored the fundamental characteristics of these cells, such as how to distinguish them from other cells in the brain, their exact location, how they develop, what genes they express and how they interact with other cells.”
These macrophages, along with other immune cells in the brain called microglia, originate outside the embryo in an area known as the “yolk sac”. As the body develops, cells migrate from the yolk sac to the brain. Using a technique called “fate mapping,” the team traced exactly where these cells ended up, and found out what causes them to become perivascular macrophages and meningeal macrophages.
“We found that meningeal macrophages develop in the same way as other microglia, and are formed during pregnancy. On the other hand, perivascular macrophages begin to form after birth and originate from meningeal macrophages. It was very unexpected, ”Masuda said. .
Thanks to their research, the team was also able to identify specific genes that lead to the generation of meningeal and perivascular macrophages.
“Identifying these genes will finally allow us to distinguish meningeal and perivascular macrophages from other microglia,” Masuda explains. “Now that we can study them individually, we can get a clearer idea of their functions.”
These findings are expected to open new avenues for understanding the role of these cells in the brain.
“Now that we know they are different, the next step is to find out their functions. As their mechanisms are identified, we hope to understand their role in pathologies such as Alzheimer’s disease, autism spectrum disorders and multiple sclerosis, ”concludes Masuda.
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