Astrocytes: the “stars” of our central nervous system

December 5th, 2023

Written by: Serena Chen

Our brain is one of the most conversational organs in our body, filled with cells that chat with each other every second of every day. These cells are categorized into various types that talk amongst each other, passing along countless messages that get organized and converted into our actions, thoughts, and memories.

The loudest of these cells are neurons, which speak to each other using electrical signals. You can think of neurons like the main callers on a phone line. When there are just two of them, one can just call the other directly and the message gets across. However, our brains are far more complex than that, and most of the time, neurons receive multiple calls at a time. So, what happens then? That is where glial cells come in. They are the phone operators – the ones that assist callers by transferring calls, answering questions, and logging information about incoming and outgoing calls. They help ensure that every call gets directed to the right place and that neurons have all the information they need to perform their functions. In fact, that was how glia, Greek for “glue”, got their name¹. Their main purpose was originally thought to be the cells that held neurons together – a neuron’s “sidekick”. However, scientists have recently found that there are much more to glia than this. For one, we now know that there are multiple subtypes of glial cells that each have their own functions in and beyond just being the mediator between neurons’ calls. And while they are not the loudest cells in our brain, what they have to say is pivotal to how our brains work.  

Astrocytes are one subtype of glial cells that have attracted much attention from scientists in recent years. They are one of the most abundant glial cells in our central nervous system and perform various important functions in health and disease. In addition to being some of the phone operators for neuronal signal transmission, astrocytes aid in neuronal development, inflammation – when your body reacts to get rid of something foreign that is potentially harmful, and recovery after brain injury². Astrocytes that fail to perform these critical functions may even contribute to diseases, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease². Growing our understanding of how these cells work will play a crucial role in developing new treatments for injury and disease, as well as further uncover the vast mysteries that lie in our brains.

Astrocytes and Neuronal Signal Transmission

Astrocytes are star-shaped cells that are essential for neurons to pass electrical signals to each other via chemical messengers called neurotransmitters. For neurotransmitters to be released from one neuron to another, neurons must maintain a balanced chemical environment inside and outside of the cell. When not transmitting electrical signals, the chemical environment allows neurons to rest and prepare for the upcoming signals, or phone calls, they will receive next. Astrocytes are extremely important for this process. For example, when a certain number of a particular chemical, like potassium, gets too high, astrocytes will help bring this down so neurons can return to their resting state⁴. This is like when you are trying to sleep, and the temperature or humidity of the room is too high and makes you uncomfortable. Someone else may help you turn the temperature back to your ideal preference. Astrocytes help ensure that neurons get the rest they need so they can always perform at their peak.

In addition to helping neurons rest, astrocytes are important when neurons are actively sending and receiving electrical signals. For instance, astrocytes often act like phone operators and intercept some neurotransmitters sent between neurons. This prevents neurons from being overwhelmed by number of messages they receive at once⁵. Also, astrocytes can send their own chemical messengers directly to neurons⁶. They do this to inform neurons about which messages are the most important and require a response.

Video. A video of calcium signaling in an astrocyte. You may know that calcium is important for your bones, but it is also important for your brain! Calcium is critical for neuronal signaling via neurotransmitters, and astrocytes help with this process. The green shows one kind of calcium signal that moves through astrocytes. The black is the background. As you can see, these signals are very fast!

Astrocytes and Inflammation

Another process astrocytes are important for is inflammation. Inflammation is your body’s protective response to injury or infection by foreign organisms like bacteria and viruses⁸, during which cells are activated to attack and remove the intruders. In the brain, astrocytes can act as inflammatory cells. When the safety of our brain is threatened, astrocytes can sense molecules released by our immune system, informing them of the ongoing problem. They can then recruit other molecules and cells to help clear the invading organisms⁹.

Astrocytes and Disease

Astrocytes are essential for many significant processes in our brain, so what happens when they malfunction? In neurodegenerative disorders such as Alzheimer’s disease, astrocytes seem to lose their normal helpful functions in the brain¹⁰. When this disease progresses, there is an abnormal accumulation of proteins inside and outside of neurons. Here, the healthy communication between astrocytes and neurons appears to be broken. Rather than helping neurons, astrocytes may interact with these abnormal proteins to promote a toxic environment and neuron death¹⁰. Currently, what exactly causes these changes in astrocytes in diseases like Alzheimer’s is unknown, but further research into how these effects can be reversed is one potential direction toward developing new treatments and cures for this disease.

Although they are some of the quieter voices in our nervous system, astrocytes help perform some of the most important functions in our brain. While they can be a neuron’s sidekick, the phone operator that ensures all messages get where they need to go, astrocytes are also crucial in our fight against infections and maintaining the overall healthy functions of our brain. While these beneficial functions of astrocytes are altered in disease, substantial ongoing research aims to discover why this takes place, so further efforts can be made toward the development of new treatments that can prevent or reverse these effects.

References

1. Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. Neuroglial Cells. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10869/
2. Lee HG, Wheeler MA, Quintana FJ. Function and therapeutic value of astrocytes in neurological diseases. Nat Rev Drug Discov. 2022 May;21(5):339-358. doi: 10.1038/s41573-022-00390-x. Epub 2022 Feb 16. PMID: 35173313; PMCID: PMC9081171.
3. Grider MH, Jessu R, Kabir R. Physiology, Action Potential. [Updated 2023 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538143/
4. Bellot-Saez A, Kékesi O, Morley JW, Buskila Y. Astrocytic modulation of neuronal excitability through K+ spatial buffering. Neurosci Biobehav Rev. 2017 Jun;77:87-97. doi: 10.1016/j.neubiorev.2017.03.002. Epub 2017 Mar 6. PMID: 28279812.
5. Mahmoud S, Gharagozloo M, Simard C, Gris D. Astrocytes Maintain Glutamate Homeostasis in the CNS by Controlling the Balance between Glutamate Uptake and Release. Cells. 2019 Feb 20;8(2):184. doi: 10.3390/cells8020184. PMID: 30791579; PMCID: PMC6406900.
6. Ota Y, Zanetti AT, Hallock RM. The role of astrocytes in the regulation of synaptic plasticity and memory formation. Neural Plast. 2013;2013:185463. doi: 10.1155/2013/185463. Epub 2013 Dec 4. PMID: 24369508; PMCID: PMC3867861.
7. Agulhon C, Petravicz J, McMullen AB, Sweger EJ, Minton SK, Taves SR, Casper KB, Fiacco TA, McCarthy KD. What is the role of astrocyte calcium in neurophysiology? Neuron. 2008 Sep 25;59(6):932-46. doi: 10.1016/j.neuron.2008.09.004. PMID: 18817732; PMCID: PMC3623689.
8. Patani R, Hardingham GE, Liddelow SA. Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration. Nat Rev Neurol. 2023 Jul;19(7):395-409. doi: 10.1038/s41582-023-00822-1. Epub 2023 Jun 12. PMID: 37308616.
9. Sanmarco LM, Polonio CM, Wheeler MA, Quintana FJ. Functional immune cell-astrocyte interactions. J Exp Med. 2021 Sep 6;218(9):e20202715. doi: 10.1084/jem.20202715. Epub 2021 Jul 22. PMID: 34292315; PMCID: PMC8302447.
10. Phatnani H, Maniatis T. Astrocytes in neurodegenerative disease. Cold Spring Harb Perspect Biol. 2015 Apr 15;7(6):a020628. doi: 10.1101/cshperspect.a020628. PMID: 25877220; PMCID: PMC4448607.

Cover photo by Serena Chen.

Video by Serena Chen.

Figure 1 by Shopify Partners on Burst.