Everyone always talks about neurons (brain cells) — neurons, neurons, neurons, but no one ever talks about microglia! But first of all, what are microglia? Microglia are part of the glial cells in the CNS (central nervous system — the brain and the spinal cord). The glial cells are split into two groups — macroglia and microglia. The purpose of the macroglia is to be the bodyguards for neurons, helping them move and develop while protecting them. The macroglia are significantly larger than the microglia, so they are named “macro,” which is a root word for large. The purpose of microglia is to be the janitors of the brain, digesting any foreign particles or materials in the brain. The name microglia is derived from the Greek words ``micro” for small and “glia” for glue. So, their name means little glue!
So what do these fascinating little cells look like? Well, as mentioned above, microglia are significantly smaller than macroglia. Microglia have two states. The steady-state (or resting state) and the active state (it is also called inflammation).
Microglia’s Origin So where do these microglia come from? Most of the other glial cells come from a layer of tissue in the embryo (a fertilized egg cell) called the neuroectoderm (“neuro” meaning brain, “ecto” meaning outer, and “derm” meaning skin), which gives rise to the brain area. But for microglia, they come from mesoderm (“meso” meaning middle, “derm” meaning skin). The mesoderm gives rise to the blood and the immune system. In addition, microglia can also come from white blood cells (called monocytes) that move around in the blood and make their way to the nervous system. But what about the yolk sac? Wasn’t that in the title of this article? Yes, microglia also have a relation to the yolk sac. The yolk sac in an embryo is a structure outside the embryo with a membrane that does various functions, including primitive hematopoiesis (the process of stem cells becoming blood cells). In the first wave of cells differentiating (primitive hematopoiesis), macrophages are created. These macrophages flood into the CNS area using blood circulation as a pathway. After the blood-brain barrier (a complex of tissue and blood vessels that keep harmful substances from getting to the brain) forms, the flow of macrophages seizes. The microglia create more of themselves using a coupled process. The process of proliferation (rapid increase in numbers) and dying is coupled, so the relevant levels of microglia stay constant. There is no interference from monocytes in dividing.
Steady State Microglia
In the steady state, the microglia have a small soma (body) housing the nucleus (the orange sphere in the picture) and long-branched processes (the extensions from the soma). The processes allow the microglia to move around using the process of chemotaxis (parts of the cell moving towards areas with a higher concentration of an attractive chemical (chemoattractant)). The purpose of resting microglia is to simply sit there and wait for trouble. The long processes branching out from the soma allow the cell to sample the interstitial fluid (a fluid that cushions and supports the brain cells), and when the microglia senses trouble, it converts to the active state. Specifically, the microglia search for inflammation. When it detects inflammation, it retracts its processes and converts to the active state. The microglia know when to convert to the active state because it recognizes molecules like viral DNA, RNA, PAMPs (pathogen-associated molecular patterns), LPS (lipopolysaccharide, brief definition), and ATP (adenosine triphosphate, the bodies’ energy molecule). These molecules bind to receptors in the processes of the microglia, activating the transition to the active state.
Active State Microglia
In the active state, microglia act pretty much like macrophages in other body parts. Macrophages are cells that move around looking for dead or damaged cells, debris, and toxic components and “eat” them. The microglia will move to places with foreign components, dead cells, damaged cells, plague, and any pathogens (bacteria, viruses, etc.) and consume them. First, the microglia will release cytotoxins, compounds that will kill the substance. One example of a cytotoxin is reactive oxygen species, these can kill bacteria. After the cytotoxin kills/breaks down the substance or cell, the microglia will engulf (phagocytose) the debris that is left over.
Microglia and Neurodegenerative Diseases
In the grand scheme of the brain, what do the microglia actually do? Microglia play a very important role in neurodegenerative diseases. Microglia are extremely important in removing plaque and assisting with diseases like Alzheimer’s disease where a specific type of plaque accumulates. In infections such as Creutzfeldt-Jakob disease, microglia are vital in removing the bacteria or viruses that caused the infection. Microglia can also remove prions, which are abnormal proteins that can cause neurodegenerative diseases. But there is also a flipside to microglia. Microglia can go too far and destroy perfectly healthy cells nearby. This can result in the release of even more inflammatory molecules, causing other microglia to kill more brain cells. In conclusion, microglia are extremely important glial cells, but further research has to be done to fully understand microglia and its implications.
