[♪ 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]
