anonymous asked:

Could you talk more about glial cells and what they do, please? It sounds really interesting!

SKIPS THE QUESTION I WAS ANSWERING TO ANSWER THIS (sorry folks that are waiting, but you’ll learn soon that scientists are fickle, easily excitable little nerds).


Glial cells haven’t gotten a lot of attention in the past eternity because scientists are rude there haven’t been many tools to study them. Traditionally, neurons have been the stars of the show- if you’ll notice, it’s called neuroscience, like neurons, not cerebroscience, like brains or neuro/glial sciences, which doesn’t really roll off the tongue. And there are plenty of reasons neuroscientists/physiologists have focused on neurons. Neurons conduct sodium/calcium currents, can propagate action potentials, send electrical and chemical signals to one another, can be huge and complicated and are what your brain uses to control the rest of your body (aka nerves). They’re fancy, they’re exciting (badum TSS), and back when people first started recording from the nervous systems of animals, were the easiest/most practical to investigate; glial cells don’t conduct sodium/potassium currents, don’t seem to have much electrical activity (at first glance), tend to be pretty small. For the longest time, all they seemed to do was clean up after neurons, insulate them to make them a bit more efficient, and provide them with necessary metabolites. Cool, but if neurons are NASA engineers, glial cells are like the janitors and service people of the HQ. Clearly important, valued, but by societal standards, not as cool to know as an aerospace engineer.

Enter calcium waves, the tripartite synapse, radial glia, and forebrain engraftment of astrocytes.

So glial cells can typically be broken down into 3 major types: schwann cells/oligodendrocytes, microglia, and astrocytes. Schwann cells/oligos (for short) are the cells that make up the myelin sheath of a neuron. If you imagine that axons (the projections/arms of neurons) are electrical wire, you can imagine that Schwann cells/oligos are the stuff that insulates them. You never see exposed copper wires where you can reach them, and neurons tend to be like that. Being insulated helps them conduct electrical signals. As a note, the difference between Schwann cells and oligos is that oligos are in the brain and Schwann cells are everywhere else (the spinal cord, for example). 

Microglia are the first defenders of the brain. They’re basically the immune system of the brain, which needs its own thing because what can enter/exit the brain is so tightly controlled (that blood-brain barrier though). As a result, your usual immune cell first responders can’t get through, and the brain would be defenseless without these microglia. Of course, because of this tight regulation, it’s very rare that diseases get into the brain in the first place (brain infections are waaaaay rarer than throat infections, eye infections, sinus infections, etc). This means that microglia are typically going around cleaning up plaques (lumps of unusable proteins) and other trash, breaking down dead/damaged/unneeded neurons and synapses, and generally going around making sure the brain is neat and tidy. When pathogens do get into the brain, they immediately go into attack mode, eating up anything that might hurt the brain and using their cytotoxins to break things down. And when the brain is damaged, if you read the TBI post, they also send signals to other glial cells, neurons, and immune cells to ask for backup or tell them what’s going on. Unfortunately, when microglia are damaged or are overactive, they can also release the same toxins they use to help the brain, causing injuries, swelling, and damage elsewhere. However, that’s in really severe cases. They’re generally really helpful, and they can even help regrow and readjust neural circuitry. 

Finally, we have astrocytes- the STAR of the show (*canned laughter*). Holy crap are astrocytes cool. They get their name from their star shape, but the name is also appropriate for something they do that we call “twinkling” (yes, that is the real name for it. Here’s a video from Smith’s lab at Stanford:

Now, that’s not actually what it looks like in the brain (these astrocytes have been made to express something that makes them light up when calcium moves through the cell, and these are in culture, on a dish), but what you’re seeing is that they do, in fact, have electrical responses to stimuli (the neurotransmitter glutamate, in this case)

In case you want to know what it looks like in neurons, here’s a video from Sur’s lab at MIT (btw neurons also use calcium, but differently):

These are neurons in the visual cortex (the part of your brain responsible for sight) of a living mouse in response to being shown the image on the top right corner. Again, neurons in your brain aren’t constantly glowing, they’ve just been genetically altered to do so here for the sake of being able to measure their activity.

You can see that the neurons respond in what look like networks, that they have larger processes, and that signals travel really far, really fast. Astrocytes are way tinier in comparison and generally slower. But the interesting thing is that, in the brain, astrocytes form something like nets (we call it tiling) that neurons send their axons through. Without going into too much detail, this basically allows astrocytes to grab onto a ton of neuron’s axons at once, so they’re able to hook into the electrical activity and respond to it. Importantly this tiling also allows astrocytes to talk to other astrocytes, meaning that when neurons are carrying all the big important infromation of the brain, astrocytes respond to it, talk to each other, and possibly modulate the signal the neurons are sending. They basically mediate a LOT of the activity going on in the brain.

Another thing you may have heard of is the synapse- basically the tiny space between the tiny bits of two neurons that are talking to each other. If you google “synapse”, you’ll see something that looks like two appendages next to each other- but recently, it’s been discovered that many synapses are actually composed of three cells (thus the name “tripartite”). Astrocytes send their tiny arms around these synaptic contacts and adjust the information that goes from neuron to neuron, then possibly feed information back to other astrocytes, or use that information to know how to adjust information flow at other synapses. They’re not sending all the cool info, maybe, but they’re twiddling with dials, making sure everything is efficient and appropriate.

…This is getting really long so I’ll try to be more concise. 

Radial glia are a type of glial cell that you don’t really have now that you’re grown, but that exist when you’re still in the womb, developing a brain in the first place. First hypothesized by Pasko Rakic (my hero) and later confirmed when we had the tecnology to test it, these cells are found to stretch their arms all the way from the very center point of what will become your brain to its outer edge and provide a structure for baby neurons to crawl up to where they need to be. The vast majority of neurons in your brain right now did this way back before you were even born, and they’re still in the same place they were when they first did this! So basically, radial glia make it possible for your brain to even get organized. Even more visually interesting, some of these cells are also necessary for the formation of sulci and gyri in the brain- that is, the wrinkles that you imagine when you think of what your brain looks like.

BASICALLY, glial cells are waaaaaaaaay more than support cells in the brain and are important for its development, function, and healing.

Now that might be all fine and dandy and fun nerdy brain stuff, but something even cooler: if you give a mouse human astrocytes, they get smarter.

Let me say that again: human astrocytes can make mice smarter.

In an absolutely beautiful, elegant, and stunning study (it’s my favorite tbh), Xiaoning Han, at the lab of Jan Nedergaard at the University of Rochester, implanted neonate mice with human derived astrocytes. These astrocytes were faster, bigger, better, and again, made mice learn faster, both from a behavioral and electrical point of view. Within a day, they were performing as well on different tasks as control mice after a week, and in many cases, they made fewer errors or performed even better with more training. These human-derived astrocytes (which were pulled from stem cells using some cool genetic and technological tricks) not only integrated into the brain structurally, but were able to alter its function– keep in mind, no changes were made to the neurons of the mouse’s brain by the experimenters.

Of course, you should always be skeptical in science, and this was one study, on a limited array of tasks, without knowledge of long term effects, requiring replication, and certainly only possible in mice at the moment, but…. that’s awesome???

So I guess a summary is required. Basically, neurons are really cool and the NASA engineers of the brain, and glial cells are superheroes with janitor day jobs. #science No, but in all seriousness, glial cells are really, really cool and a lot of neuroscientists are starting to investigate them too. Your brain isn’t just neurons, and all those “support” cells are much more impressive than they’ve been given credit. I could probably go on and on for hours, but you get the idea- and if you’re interested, there are plenty of papers you can read online (try looking up the scientists I mentioned above ^). 

I hope this somewhat appeased your curiosity!

–Mod Nopal 🌵

(Image caption: Without the prion proteins, the so-called Schwann cells around the sensitive nerve fibers no longer form an insulating layer to protect the nerves. Credit: NatureReview / Neuroscience)

Impact of prion proteins on the nerves revealed for the first time

When prion proteins mutate, they trigger mad cow and Creutzfeldt-Jakob disease. Although they are found in virtually every organism, the function of these proteins remained unclear. Researchers from the University of Zurich and the University Hospital Zurich now demonstrate that prion proteins, coupled with a particular receptor, are responsible for nerve health. The discovery could yield novel treatments for chronic nerve diseases.

Ever since the prion gene was discovered in 1985, its role and biological impact on the neurons has remained a mystery. “Finally, we can ascribe a clear-cut function to prion proteins and reveal that, combined with particular receptor, they are responsible for the long-term integrity of the nerves,” says Professor Adriano Aguzzi from the Neuropathological Institute at the University of Zurich and University Hospital Zurich. The present study therefore clears up a question that researchers have been puzzling over for 30 years, but ultimately went unanswered.

Prions are dangerous pathogens that trigger fatal brain degeneration in humans and animals. In the 1990s, they were responsible for the BSE epidemic more commonly known as mad cow disease. In humans, they cause Creutzfeldt-Jakob disease and other neurological disorders that are fatal and untreatable. Meanwhile, we know that infectious prions consist of a defectively folded form of a normal prion protein called PrPC located in the neuron membrane. The infectious prions multiply by kidnapping PrPC and converting it into other infectious prions.

Absent prion proteins cause nerve diseases

For a long time, it remained unclear why we humans – like most other organisms – have a protein in our neurons that does not perform any obvious function, yet can be extremely dangerous. Aguzzi has spent decades researching this issue and examining the theory that animals without the PrPC gene are resistant to prion diseases. But what are the repercussions for the organism if the prion protein is deactivated?

A few years ago, Aguzzi and his team discovered that mice without the PrPC gene suffer from a chronic disease of the peripheral nervous system. The reason: The so-called Schwann cells around the sensitive nerve fibers no longer form an insulating layer to protect the nerves. Due to this insulating myelin deficit, the peripheral nerves become diseased, potentially resulting in motoric disorders in the motion tract and paralysis.

The researchers have now gone one step further in the lab: In a new study, Alexander Küffer and Asvin Lakkaraju clarify exactly why the peripheral nerves become damaged in the absence of the prion protein PrPC. They discovered how the PrPC produced by the neurons docks onto the Schwann cells: namely via a receptor called Gpr126. If the prion protein and the receptor work together, a particular messenger substance (cAMP) which regulates the chemical interaction in the cells and is essential for the integrity of the nerve’s protective sheath increases. Gpr126 belongs to the large family of “G-protein-coupled receptors”, which are involved in many physiological processes and diseases.

30-year-old research question finally answered

This discovery solves a key question that has long puzzled neuroscientists and points towards future applications in hospitals. “If you want to deactivate the prion protein PrPC fully for potential Creutzfeld-Jakob disease treatments, you need to know the potential side effects on the nerves in the future,” explains Aguzzi. Moreover, the present results on the effect of PrPC at molecular level could yield a new approach for peripheral neuropathy. Currently, there are only extremely limited therapeutic options for these chronic debilitating diseases of the nervous system.