Microglia: Guardians of the Brain

Ruth Jones | 9 JUL 2018

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.

Edited by Sam Berry & Chiara Casella

What is neuroimmunology and why should I care?

Dr Niels Haan | 15 AUG 2016

Everybody knows about the immune system, right? You get an infection and your body mobilises its army of immune cells and fights off the invaders. You get a fever, feel awful for a while, then things get back to normal. However, in the brain, it doesn’t work that way. In immunology, the brain is called privileged. This doesn’t mean its parents had money and it went to a better school than you; it means it’s excluded from the normal immune response. In this post, I introduce you to the wondrous world of neuroimmunology, the study of the immune system in the brain. Hopefully this will whet your appetite for a longer article exploring this more in depth, which will be coming out later.

The brain is separated from the rest of the body and the blood circulation by the blood-brain barrier, allowing the brain to be selective with what it lets in, and protecting it from infection. However, this also means the usual immune cells normally can’t get in. Luckily for us, the brain has its own immune cells, microglia. These cells are continuously patrolling your brain for anything that shouldn’t be there, and will attack and clear out any infections. Although this is an important role, unless you’re unlucky enough to contract something like meningitis, most neuroimmunological processes actually do not involve infection.

Microglia

So why should you care about this? You should care because neuroimmunology is involved in pretty much every brain process and disease investigated so far. The most obvious ones are autoimmune diseases of the central nervous system, such as multiple sclerosis, where the immune system incorrectly recognises your own cells and proteins as something foreign to your body and attacks them. However, there are many more diseases with neuroimmunological involvement.

In neurodegenerative diseases such as Alzheimer’s or Parkinson’s, microglia are activated and clear out the many dying cells. However, the signalling factors microglia secrete can cause more neuronal dysfunction and cell death, creating a vicious circle. Activation of immune cells has also been found in many psychiatric diseases such as chronic depression and schizophrenia, but we don’t yet have a clear idea of their roles in these conditions. However, the immune response in some of these diseases is now starting to be studied as a target for potential new treatments.

It is easy to view the immune system as something that only kicks into action during infections or disease. It is, in fact, working all the time and is part of the brain’s normal development and maintenance. Neurons continuously make new connections and lose old ones. Microglia, the immune cells of the brain, are responsible for clearing out old and faulty connections, ensuring your neurons connect the way they should.  The immune system is also closely involved with the formation of new neurons. These roles can again be affected by disease. For instance, my own research has shown that neuroinflammation in chronic epilepsy may be responsible for lower numbers of new neurons and the memory problems patients suffer from.

Neuroimmunology is still a rapidly expanding field, and we are continuously finding new roles for immune cells and factors in the brain. In fact, only last month, research suggested that immune factors are involved in the regulation of social behaviour in a range of animals. (Note: you could try this as an excuse for being antisocial next time you have a cold. Don’t blame me if it doesn’t work though.) Having now hopefully convinced you that you should care about neuroimmunology, stay tuned for a longer post exploring its roles in detail!