Microglia: Guardians of the Brain

By Ruth Jones

Edited by Sam & Chiara

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Our Immune System works hard to protect us from unwanted bugs and help repair damage to our bodies. In our brains, cells called Microglia are the main immune players. Microglia are part of a group of immune cells called Macrophages, which translates from Greek as “big-eaters”. Much like students faced with free food, macrophages will eat just about anything, or at least anything out of the ordinary. Whether it’s cell debris, dying cells or an unknown entity, macrophages will eat and digest it. Microglia were first discovered in 1920’s by W. Ford Robertson and Pio del Rio-Hortega. They saw that these unidentified cells seemed to act as a rubbish disposal system. Research into these mysterious cells was side-lined during WWII, but was eventually picked up again in the early 1990’s.

When I think about how microglia exist in the brain, I am always reminded of the blockade scene in Marvel’s Guardians of the Galaxy. Each “ship” or cell body stays in its own territory while its branches extend out to touch other cells and the surrounding environment. The microglia ships can then use their branches to touch other cells or secrete chemicals to communicate, together monitoring the whole brain.

ruthNova Core Blockade Scene © Guardians of the Galaxy. (2014). [DVD] Directed by J. Gunn. USA: Marvel Studios.

Microglia have evolved into brilliant multi-taskers. They squirt out chemicals called chemokines that affect the brain’s environment by quickly promoting inflammation to help remove damaged cells, before dampening inflammation to protect the brain from further damage. They also encourage the growth of new nerve cells in the brain and can remove old “unused” connections between neurones, just like clearing out your Facebook friend list. Microglia keep the brain functioning smoothly by taking care of and cleaning up after the other cells day in, day out.

Today, microglia are a trending topic, believed to play a part in multiple brain diseases. Genetic studies have linked microglia to both neuropsychiatric disorders like autism and neurodegenerative diseases such as Alzheimer’s disease.

Do microglia help or hurt in Alzheimer’s disease? This is a complicated question. Scientists have found microglia can both speed-up and slow-down Alzheimer’s disease. Scientists have thought for a while that in disease these microglia “ships” are often destroyed or are too aggressive in their efforts to remove sticky clumps of Αmyloid-β protein (a big problem in Alzheimer’s disease).

What is going on in the Alzheimer’s disease brain? Recent advances in technology mean scientists are now starting to discover more answers. One problem when working with microglia is they have a whole range of personalities, resulting in a spectrum of protein expression and behaviour. Therefore, when you just look at the entire microglial population you may miss smaller, subtle differences between cells. It is likely that microglia don’t start out as “aggressive” or harmful, so how can we see what causes microglia behaviour to change?

Luckily a new process called “single-cell sequencing” has been able to overcome this. An individual cell is placed into a dish where the mRNA, the instructions to make protein, can be extracted and measured. This means you can compare the variation in the entire microglia population, which could make finding a “trouble-maker” microglia easier in disease. This process could also be used to see how individual cell types change across the course of Alzheimer’s disease.

In the future, by looking in detail at how these individual microglia “guardians” behave, scientists can hopefully begin to unravel some of the mysteries surrounding these fascinating and hugely important cells in both health and across all disease stages.

 

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