Microglia: An essential sanitation crew
“We have a 2319”!!! There’s a contamination alert in Monster’s Inc.! The unassuming and innocent George Anderson (image on right) had no clue that a human sock was attached to his back. The monsters around him are terrified and no monster dares to come within a foot of him. The ceiling windows blast open and the Child Detection Agency (CDA) burst through the open windows to eliminate the contamination. Hundreds of CDA employees surround George and extract the human sock from his back and destroy the contamination.
Similarly, the human brain also contains a CDA, albeit less yellow. The human nervous system relies heavily on tiny immune cells called microglia. Like the Monster’s Inc. CDA sanitation crew, microglia ensure the brains environment is healthy. While the CDA sanitation crew targets human socks and human toys, microglia scavenge for damaged neurons and infectious materials that could be harmful to the delicate nervous system. Microglia are incredibly important, so much so that they out number neurons by a ratio of 10:1.
In the event that a foreign infectious agent enters the brain, microglia assemble and react quickly to destroy it before it has an opportunity to damage neurons. A part of this process includes producing large volumes of a gas called nitric oxide (NO) that is made by an enzyme called inducible nitric oxide synthase or iNOS. NO is an important messenger molecule in the body and as a gas, it can easily diffuse into adjacent cells. Previous studies have found that NO can inhibit the proliferation (rapid replication) of different cell types. However, NO’s effect on microglia, a large producer of NO, remained unclear. Experiments performed by Dr. Maksoud help shed light on how NO regulates microglia proliferation.
Before we uncover how iNOS and NO effect microglia proliferation, what does proliferation mean and why does it matter in the human nervous system? When microglia activate in response to a foreign/pathogenic entity, they replicate rapidly to minimize the threat. The threat can be small or large, regardless of its initial size, microglia will proliferate. Boo from Monster’s Inc. was a child that accidentally made it into the Monster’s Inc. universe and her presence caused a cascade of events. She was not a threat by any means however, because she was foreign to the Monster’s Inc. world, hundreds of the CDA employees set out to capture her and remove her from their world. Similarly, microglia will increase in number and target the foreign or pathogenic entity head on and stop it before it can cause any damage to neighbouring neurons.
Dr. Maksoud’s study treated microglia cultures and revealed that iNOS and NO play a key role in regulating proliferation within microglia. Specifically, iNOS activity and NO signalling restrict microglia proliferation. These results are in line with previous studies that investigated NO’s effect on other cell types in the body. Without NO, it is difficult to inhibit microglia proliferation and consequently, difficult to reduce inflammation. Imagine hundreds of the CDA employees running rampant searching for Boo and causing destruction and chaos in their path.
Inflammation is a double-edged sword. In short-term conditions, it protects the infected area from other invaders while it promotes healing. However, chronic inflammation can cause more harm and damage neighbouring cells. Chronic inflammation in nervous tissue has been linked to diseases such as Parkinson’s disease and Alzheimer’s disease. Therefore, it is important for microglia to control their activation. NO acts as an important regulator of microglia and this study can help pave the way for future studies to explore NO and microglia in disease models.