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When talking about the brain, neurons have been dazzling scientists for a long time. But behind every successful neuron is a glial cell - particularly one type of them: microglia.

Hosted by: Brit Garner
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[♪ INTRO].

When we talk about mental illness, or anything  else brain-related, we usually talk about neurons. They’re the nerve cells that  send electrochemical messages   that allow you to think or go for  a hike or watch science videos.

And for a long time, scientists have been  dazzled by their electric personalities. But neurons are only half the story. We have an almost equal number of a whole  other family of brain cells called glia, which perform all kinds of  supportive functions for neurons,   from pruning them to keeping them safe.

In fact, you could say that behind every  successful neuron is a glial cell.  Historically, these things haven’t  gotten the respect they deserve. But now, researchers are realizing  how amazingly important they are. And that’s especially true for  one type of them: microglia.  Microglia act as the brain’s janitors, nurses,   paramedics, police, judges,  juries, and executioners.

They may play a big role in depression,  obsessive-compulsive disorder, bipolar disorders, Parkinson’s,  Alzheimer’s, autism, and more. And did we mention they can  shape-shift and eat neurons? It’s time to meet your microglia.

Scientists have known about  glial cells since the 1920s, but they often overlooked them in favor  of those much flashier cells, the neurons. That’s partly because glia don’t produce  electrical impulses like neurons do, so they’re not as obviously interesting. It’s also because, when researchers first  started to study the nervous system, the dyes they used to stain brain  tissue didn’t allow them to see glia   as well as they could see neurons.

And on top of that, the actions of glial  cells and neurons are so intimately connected, it’s really hard to tell which one is doing what. So in the end, many scientists  gave most of the credit to neurons,   and they thought glia were boring do-nothings. In fact, the word “glia” is  related to the word “glue,” because researchers believed they just sat  there, sticking brain tissue together.  But thanks in part to better imaging techniques, researchers are starting to appreciate  these underdogs, especially microglia.

Today, we know that microglia are  fundamentally different from other brain cells. Unlike neurons and other glial cells,   they emerge in an embryo from the same family  of stem cells that turn into white blood cells, your body’s immune system warriors. Then, a few days after conception,   the microglia migrate through the blood  to the developing brain, where they stay.

That makes them part of your immune system! And it also explains some  of the things they can do. One of microglia’s most important tasks  is cleaning out the junk in your brain.

That’s why so many sources  call them the brain’s janitors. Microglia look for dead cells, pathogens, and  harmful protein clusters that might cause disease. And while research summaries and science blogs   often say microglia “mop up”  or “sweep away” this garbage, what’s really happening is much, much cooler.  In their normal state, microglia have  several protruding, spidery arms that grope around looking for dangerous  invaders or damaged neurons.

When they find a problem, they move toward it. Then, they pull in their arms... turn into  a sort of blob... and eat the problem. They swallow it up, then transfer  whatever they’ve eaten to their lysosomes, tiny, internal sacs that act like stomachs.

Lysosomes contain digestive enzymes  that break down larger molecules into smaller ones that feed the microglia. Microglia can even morph into various  shapes depending on what they’re attacking. For example, when they’re fighting syphilis,  they turn into a sort of rod shape.

And while scientists don’t know why that  helps, exactly, it’s apparently useful. Microglia aren’t just  shape-shifting housekeepers, though. You can also think of them as the brain’s nurses.  They’re constantly reaching their arms around to  touch neurons and see if they’re working properly, like a nurse taking a patient’s  pulse and vital signs.

If they notice a neuron releasing chemicals that  signal something is wrong, they eat the neuron.  Okay, maybe they aren’t so much like nurses. Or at least… good nurses. But, as weird as it is to think that there are   spidery, blobby things eating parts  of your brain, it’s really important.

For one, it helps your brain develop. When you’re a baby, you have trillions more  synapses than you end up with as an adult. Synapses are the connection  points between your neurons.

And during childhood and adolescence, you go  through a process called synaptic pruning. Often, sources just generally say it’s the time  where your brain gets rid of unneeded synapses. But your microglia are big players here.

They move around monitoring  your neurons and synapses. If the connection is functioning well,  microglia can secrete chemicals that stimulate the synapse and make  the connection even stronger.  But if the synapse is functioning poorly… you can  probably guess where this is going… they eat it.  Classic microglia. Scientists have even used high-resolution  imaging to watch this process in action in mice.

They’ve seen microglia reach out  to synapses with their little arms, and then suddenly, pieces of synapse  were digesting inside the microglia. So essentially, these cells act as judge,  jury, and executioner for your neurons. And they do this by eating your brains.  But beyond all this, as if this weren’t  enough, these cells also keep you safe.

They help protect your brain from nasty stuff  like viruses, and they don’t always work alone.  Remember their cousins, the white blood cells? Well, when microglia encounter a  dangerous invader, like a virus, they can produce proteins called cytokines  that recruit white blood cells and allow them to break through the blood-brain  barrier and help attack the virus.  So, overall, microglia are  so important for our brains. But you know how it goes: With great  power comes great responsibility.   And microglia aren’t always perfect.

In fact, lots of things can  mess with their activity. For example, some scientists think negative  experiences in childhood like infection, abuse, and neglect could permanently  alter microglia’s behavior. These experiences could lead the  brain to release stress hormones, which could ultimately prime the microglia  to be hypersensitive in the future.

And that could make the cells less  able to perform their helpful functions   and more prone to eating healthy neurons. Microglia behavior can also be  altered by countless other factors, trauma, aging, diet, stress,  and sleep problems among them. Basically, these factors all lead  to chemical changes in the brain   that can influence what these cells are up to.

Stress, for example, causes our  bodies to produce norepinephrine,   a hormone neurons use to send signals. And a 2019 study published in Nature Neuroscience   showed that when mice were  releasing high levels of it, their microglia stopped repairing  injuries and rewiring neurons. All of these factors can  cause microglia to go haywire.

And evidence is mounting that these overzealous   cells can cause a range of  neurological conditions. Like, research suggests that depression  can be caused by both underactive   and overactive microglia. The thinking is that the overactive  cells could destroy healthy synapses,   and the underactive cells would… well, it’s not clear what they’d be doing,   but several depression patients have been  found to have lower microglia activity, so scientists think /something/ is happening.

Regardless, this may explain why  both electroconvulsive therapy   and anti-inflammatories can  alleviate depression symptoms:. Electroconvulsive therapy  stimulates sluggish microglia,   while anti-inflammatories  tone down over-eager ones.  Dysfunctional microglia are also linked  with obsessive-compulsive disorder,   bipolar disorders, anxiety, and other psychological conditions, maybe for   similar reasons, or because of  a genetic change in the cells.  They even seem to be involved in autism. This seems to play out in a few  ways, but to give one example, autistic children tend to have a lot more synapses  in some parts of the brain than neurotypical kids, possibly because their microglia didn’t  eat as many synapses during pruning.

So their brains are synchronized differently,   which could influence how  they interact with the world. Microglia are even implicated in  Alzheimer’s and Parkinson’s diseases, both of which are associated with  the death of neurons and synapses. Although, like many things with these  illnesses, the research is complicated.

Like, when it comes to Alzheimer’s specifically, scientists are hotly debating whether  microglia are helpful, harmful, or both. Because sure, they can eat the plaques  that contribute to the disease’s symptoms. But they can also go too  far and eat healthy neurons,   possibly initiating the disease  and driving its progression.

And honestly, all of that is  just the tip of the iceberg. Microglia may play important roles in   numerous other psychiatric and  neurological conditions, too. But do note that we don’t see unusual microglial  activity in everyone with psychiatric conditions, so it’s not like they offer  some universal treatment.

And anyway, at this point,   scientists don’t really know how to rein in  rogue microglia or fine-tune their behavior. Though some are starting to try. For example, to treat Alzheimer’s,   researchers in Arizona have manipulated  microglia with choline supplementation.

Choline is a common nutrient found naturally  in foods like beef, eggs, and soybeans.  And in their 2019 study, the researchers  found that lifelong choline supplementation reduced microglia activity and improved  memory in mice with Alzheimer’s-like symptoms. But that’s just mice, so don’t get too excited. Especially since they live  much shorter lives than humans, it’s hard to say exactly how  these results translate to us.

Ultimately, there’s still a lot we need to learn  about microglia and how we can manage them.  The good news is that, because these cells have   their little arms and fingers  in so many neurological pies, studying them offers an opportunity to  understand a wide variety of conditions. And along the way, I’m sure we’ll discover  more fascinating things about these cells. Thanks for watching this episode of SciShow Psych!

Microglia are so interesting, but we  couldn’t have gone as deep into the research without the support of our patrons on Patreon. They allowed us to spend more time on this video. So to all our patrons, thanks for being here!

If you want to learn more  about our Patreon community and how to help us keep making free educational  content online, you can go to Patreon.com/SciShow. [♪ OUTRO].