Astrocytes: The Unsung Heroes of the Brain

Post by Trisha Vaidyanathan

What are astrocytes?

Astrocytes are star-shaped cells that are found throughout the brain and contain thousands of very fine branches. Astrocytes are the largest type of a neural cell called “glia”, which is the Latin word for “glue,” because scientists originally thought they simply existed to hold the brain together. However, the field of astrocyte biology has exploded in recent years, and while many mysteries remain, it is now well-appreciated that astrocytes serve many critical functions in the brain. 

Astrocytes are an essential component of the synapse

Canonically, the neuronal synapse includes two players: the pre-synaptic neuron and the post-synaptic neuron. However, we now know that there is a third player — the astrocyte — resulting in what is called the “tripartite synapse”. Most neuronal synapses are enveloped by an astrocyte branch. By “hugging” the neuronal synapse, astrocytes can both monitor what is happening via different receptors and directly manipulate the synapse. Astrocytes can manipulate synapses in several ways, including altering ion and neurotransmitter concentrations via transporters or by releasing their own signaling molecules. Indeed, astrocytes are necessary for synapse formation, maintenance, elimination, and plasticity.

Astrocytes provide energy to the brain

Neurons require a massive amount of energy in the brain, and astrocytes take on the job of supplying that energy. Astrocytes contact blood vessels through special branches called “end-feet” where they help form the blood brain barrier, regulate blood flow, and, importantly, take in glucose from the blood. Astrocytes either store glucose as glycogen, or convert it into lactate. Lactate is then shuttled directly into hungry neurons, where it is rapidly converted into ATP, the energy currency of the cell. Astrocytes dynamically regulate glucose uptake, storage, and lactate shuttling to match the energy demands of the brain and regulate neuronal activity.

Astrocytes respond to injury and disease

A large body of evidence has demonstrated that astrocytes are able to react in the presence of disease or injury. When astrocytes become “reactive” they change their shape, gene expression, and function. Reactive astrocytes have been found in response to most types of brain insults, including traumatic brain injury, viral infections, stroke, epilepsy, neurodegenerative diseases, autoimmune disorders, cancer, and psychiatric diseases.

There is no single definition of a “reactive astrocyte” and the response varies with the type of disease/injury and severity. Interestingly, in some instances, the reactive state can be beneficial, while in other instances it can exacerbate the disease or injury. There is still much to understand about astrocyte reactivity and what drives the astrocyte to either help or hurt.

Astrocytes control circuits and behavior

Astrocytes have thousands of fine branches that allow them to communicate with many cells at once. A single astrocyte can simultaneously contact up to 100,000 synapses in the mouse brain and two million in the human brain. As such, they are uniquely suited to regulate larger neuronal circuits. The recent development of new tools has allowed scientists to identify a critical role for astrocytes in controlling many different circuits and behaviors. Astrocytes have been shown to play a pivotal role in behaviors like memory, learning, sleep, feeding, emotional regulation, motor behavior, and decision making. Precisely how astrocytes regulate these complex circuits and behaviors remains to be understood, but it’s becoming increasingly clear that astrocytes are critical to the bigger picture of the brain and behavior.

What don’t we know about astrocytes?

Relative to neurons, our understanding of astrocytes lags far behind. However, newer tools are allowing astrocyte biologists to begin exploring some basic questions about these long-ignored cells. New microscopes and genetically encoded sensors are providing insight into how astrocytes signal to the rest of the brain using calcium. New molecular tools are revealing unique features of human astrocytes that may be critical to their role in disease and injury. Lastly, new evidence suggests astrocytes may not be just a single class of cell, but instead may have specialized functions, much like different neuron subtypes.

While there is still a lot we don’t know about the fundamental functions of these cells, new advances are being made rapidly and it is becoming increasingly clear that astrocytes are essential to brain function.

References +

Chung, Won-Suk, Nicola J. Allen, and Cagla Eroglu. "Astrocytes control synapse formation, function, and elimination." Cold Spring Harbor perspectives in biology 7.9 (2015): a020370. DOI: 10.1101/cshperspect.a020370

Hasel, Philip, and Shane A. Liddelow. "Astrocytes." Current Biology 31.7 (2021): R326-R327. DOI: https://doi.org/10.1016/j.cub.2021.01.056

Kofuji, Paulo, and Alfonso Araque. "Astrocytes and behavior." Annual review of neuroscience 44 (2021): 49-67.DOI: https://doi.org/10.1146/annurev-neuro-101920-112225

Lawal, Oluwadamilola, Francesco Paolo Ulloa Severino, and Cagla Eroglu. "The role of astrocyte structural plasticity in regulating neural circuit function and behavior." Glia 70.8 (2022): 1467-1483. DOI: https://doi.org/10.1002/glia.24191

Magistretti, P., Allaman, I. Lactate in the brain: from metabolic end-product to signalling molecule. Nat Rev Neurosci 19, 235–249 (2018). DOI: https://doi.org/10.1038/nrn.2018.19

Sofroniew, Michael V., and Harry V. Vinters. "Astrocytes: biology and pathology." Acta neuropathologica 119 (2010): 7-35. DOI: https://doi.org/10.1007/s00401-009-0619-8