Three types of brain cells: astrocytes in red, pyramidal neurons in green, and microglia cells in blue. Credit: selvanegra/ iStock / Getty Images Plus.
Researchers have discovered that a receptor found in immune cells in the brain, known as microglia, controls the development and maturation of memory areas, and could have a role in Alzheimer’s disease. The result adds to growing evidence that immune cells in the brain do not only protect neurons from damage, but communicate with them to ensure their correct functioning of the brain.
“We found that when a microglial receptor called TREM2 is not functioning properly, memory neurons in the hippocampus show abnormalities in their energy metabolism during development, with long-lasting consequences,” explains Michela Matteoli, professor at Humanitas University in Milan, and coordinator of the study, published in Immunity1. The hippocampus is involved in the consolidation of memories and is known to be damaged in the brains of Alzheimer’s patients. The researchers conducted studies on animals and found that when TREM2 is missing in microglia, neurons have fewer mitochondria — organelles that are the ‘energy powerhouses’ of the cells – with reduced functionality.
If confirmed in human models, this result could be important in the study of neurodevelopmental and neurodegenerative diseases. Variants of TREM2 were already associated with increased susceptibility to Alzheimer's disease.
“One of our future challenges is to find out how TREM2 and the microglia could send the information to the neuron,” Matteoli explains. “One hypothesis is that TREM2 releases some factors such as cytokines that act as messengers. Another is that the communication between microglia and neurons involves a physical contact”. Matteoli says the group will begin to study the latter in more detail, through a collaboration with a team in Budapest that has already demonstrated contacts between microglia and neurons at embryonic stages using high-resolution microscopy techniques.
“This discovery is interesting for future research on cognitive performance and memory, because while the role of microglia in memory has been known for many years, this is the first time that researchers have identified a molecular button for memory in TREM2, that was previously thought to play only a role in immune surveillance,” says Roberto Furlan, director of the Neurological Institute of San Raffaele Hospital in Milan.
