Newswise – Microglia – the brain’s immune cells – plays a primary role in removing cell debris from the brain. According to a recent study by a research group led by the University of Nagoya in Japan, another type of brain cell, called an astrocyte, is also involved in removing debris to support microglia. The find, recently published in The EMBO Journal, could lead to new therapies that accelerate the removal of cellular debris from the brain and thereby reduce the damaging effects of the debris on surrounding cells.
Even in a healthy brain, neurons die at a certain rate, which increases with age. As dead cells and cell debris build up, they damage surrounding cells, which in turn accelerates neuronal death and causes neurodegenerative diseases such as Alzheimer’s disease. Microglia – the brain’s “phagocytes” (a type of cell that swallows and absorbs bacteria and cellular debris) – works to eliminate the danger, but sometimes the debris overwhelms the microglia. This has led to suggesting that another mechanism that helps remove cellular debris is at work.
To clarify the nature of the alternative debris removal mechanism, a research team led by Dr Hiroshi Kiyama and Dr Hiroyuki Konishi of the University of Nagoya Graduate School of Medicine first investigated what would happen to microglial debris in the brains of mouse models in what microglia death was induced. As expected, the team observed that the dead microglia were eliminated, indicating that another phagocyte was indeed at work.
The researchers then analyzed the expression of the molecules in the brain of the mouse models and identified astrocytes that play a role in removing microglial debris. Then, using mutant mice with phagocytosis-impaired microglia, they examined how astrocytes work when microglia are not functioning properly. The results showed that nearly half of the cellular debris was engulfed by astrocytes, not microglia. This indicates that astrocytes have the potential to compensate for microglia dysfunction.
The team concluded that not only are astrocytes capable of engulfing cellular debris, but they are also likely to actually do so when the microglia are not functioning properly.
The team therefore intends to clarify how astrocytes recognize microglia dysfunction and unfold their phagocytic function. Drs. Kiyama and Konishi say, “Further investigation into how to control astrocytic phagocytosis may lead to new therapies that accelerate the efficient removal of debris from elderly or injured brains.”
The paper, “Astrocytic phagocytosis is a compensatory mechanism for microglia dysfunction”, was published in The EMBO Journal on 22 September 2020 at DOI: 10.15252 / embj.2020104464.
Information about the University of Nagoya, Japan
The University of Nagoya has a history of around 150 years, with its roots in a temporary medical school and hospital established in 1871, and was formally established as Japan’s last Imperial University in 1939. Although modest in size compared to the Japan’s largest universities, Nagoya University has pursued excellence since its founding. Six of Japan’s 18 Nobel laureates since 2000 have done all or part of their Nobel Prize-winning work at the University of Nagoya: four in Physics – Toshihide Maskawa and Makoto Kobayashi in 2008, and Isamu Akasaki and Hiroshi Amano in 2014; and two in Chemistry: Ryoji Noyori in 2001 and Osamu Shimomura in 2008. In mathematics, Shigefumi Mori won the Fields Medal at the University. Other important discoveries have also been made at the University, including the Okazaki DNA fragments of Reiji and Tsuneko Okazaki in the 1960s; and the exhaustion forces of Sho Asakura and Fumio Oosawa in 1954.
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