Microglia Cells May Promote New Synapse Formation Through Engulfing Extracellular Matrix

In order to create new memories, the brain cells must first find each other. Small protrusions from the ends of the neurons’ long branched antennae connect these neurons together so that they can communicate. The ports where these cells communicate are called synapses, and trillions of synapses are found throughout the brain, which allows us to present new knowledge. However, scientists are still finding out how these connections respond to new experiences and information.

In recent years, scientists have discovered that specialized immune cells in the brain, so-called microglia, can help remove unnecessary connections between neurons, possibly by engulfing synapses and breaking them down. Instead, new study found that microglia can also promote the formation of new synapses through the dense protein network between phagocytes, so that neurons can find each other. If scientists continue to study this new role of microglia, they may eventually find new therapeutic targets in some memory disorders.

Neurons live in a gel-like network composed of proteins and other molecules, which helps maintain the three-dimensional structure of the brain. This type of scaffold is collectively called the extracellular matrix (ECM) and has long been overlooked in neuroscience. For decades, scientists have focused on neurons, and more recently on cells that support neurons, to a large extent that the extracellular matrix is not important.

However, neurobiologists are beginning to realize that the extracellular matrix, which accounts for about 20% of the brain, actually plays a role in important processes such as learning and memory. For example, at a certain stage of brain development, the solidified extracellular matrix seems to put the brakes on the rapid turnover of new neuron connections in infants. It seems that the priority processing tasks of the brain have been shifted from adapting to the new world around it extremely quickly to more stable maintenance of knowledge. Scientists also want to know whether the rigidity of the extracellular matrix in old age may, to some extent, cope with the memory challenges brought about by aging.

For the first time, scientists realized that extracellular matrix is very important to their research on the hippocampus, which is a brain structure that is essential for learning and memory. Given the knowledge that microglia can swallow outdated synapses, they expected that disrupting the function of microglia would lead to an increase in the number of synapses in the hippocampus, however, the number of synapses has fallen. Where they thought they would find fragments of synapses broken down in the “belly” of microglia, they found fragments of the extracellular matrix.

This study found that microglia will wait for signals from neurons (an immune molecule called IL-33), the arrival of this signal indicates that it is time to form new synapses. When these researchers used genetic tools to block this signal, the microglia failed to perform their phagocytosis of the extracellular matrix, which resulted in fewer new connections between neurons in the mouse brain and made the mice difficult to remember certain details for a period of time. When they increase the IL-33 signal level, the number of new synapses increases. In older mice, brain aging has slowed the formation of new connections, and increasing IL-33 levels can help push the number of new synapses to younger levels.

This research may be important for understanding memory problems seen in age-related diseases such as Alzheimer’s disease. Besides, these findings may also be important for certain types of emotional memory problems in anxiety-related disorders.

Creative Bioarray, the world’s leading biotechnology products and services provider focus on accelerating life science research, recently announced the release of its Microglia Cells.