Amidst billions of connections with their neighbors, neurons fire electrical and chemical information at each other at enormous speed, akin to a game of laser tag with 86,000,000,000 players. Oligodendrocytes join in, and plaster everything with play dough-like myelin, creating the messiest, most complex playground that is our brain. But, somebody needs to clean up after the children. Enter astrocytes.
Stellar as their name implies, astrocytes are star-shaped cells with many appendages that take care of the rest of the central nervous system. Be it to direct axons to their destination, sweep the brain and repurpose signaling chemicals, feed and hydrate neurons or apply band-aid to their wounds, they are the true and tireless janitors of the brain.
Astrocytes derived from mouse brain. Credit: Archontia Kaminari
Several forms of astrocytes exist in the central nervous system. Fibrous astrocytes are usually located in the white matter of the brain, and have a fairly simple design. They anchor themselves to the walls of brain blood vessels, providing structural stability and nourishment to the innermost neurons. Protoplasmic astrocytes are the most prevalent type. They are found in gray matter and exhibit short and highly branched appendages that envelop synapses and travel paralell to axons, providing structural support. One such astrocyte can communicate with more than 2 million synapses, tidying up the mess the neurons make after each information exchange.Neurons trade punctuality for speed, and some information gets lost, regardless of how ingenious and tight the synapses are. Luckily, the janitors always keep watch and are ready to mop the space surrounding the synapses of any and all neurotransmitters that leak out. Radial astrocytes (or radial glia) are cells that traverse the many layers of the brain. One of their processes is rooted in the outermost protective layer of the nervous system called meninges, while the other makes its way to the deepest parts of gray matter. Their unique shape is most important in neural development, when they help with neuron migration, directing each neuron to its final destination. while the other makes its way to the deepest parts of gray matter. Their unique shape is most important in neural development, when they help with neuron migration, directing each neuron to its final destination. while the other makes its way to the deepest parts of gray matter. Their unique shape is most important in neural development, when they help with neuron migration, directing each neuron to its final destination.
All three forms help protect the nervous system's edges by reinforcing the blood-brain barrier, brain's shield located just beneath the skull.
For the longest time, neurons have been thought of as the sole proprietors of our brains, and the only cell line that mattered. As the focus of scientific community shifted from this mythical image of all-purpose neurons towards other cell types, astrocytes have emerged as clear winners of Oscar for the best supporting actors.
Ask the janitor
If you ever need to find anything in a vast building complex, ask the janitor. The same is true in the brain. If anything needs to be done, astrocytes are there to do it.
They actively support synapses between neurons by centering them and enveloping their astral appendages around them. This third-party support mechanism for an otherwise one-way information transfer has been proposed in 1999., and named the tripartite synapse. It consists of a sender neuron (presynaptic neuron), receiver neuron (post synaptic neuron) and the enveloping astrocyte appendage. The three-way system has the added benefit of electrical impulse regulation which also sends feedback information to the presynaptic neuron. In doing so, astrocytes can fine-tune the amount of electricity (information) coarsing through them.
Model of the tripartite synapse. Credit: Karine Guimaraes
Additionally, astrocytes feed the surrounding cells. Information delivery is hard work, and neurons are gluttonous and very needy. Lucky for us, astrocytes are always happy to provide a quick snack to a neighboring neuron in form of glucose or lactate. In case of food shortage, they can also raise alarms, making our stomach rumble and us crave that extra piece of chocolate. They can then widen the surrounding blood vessels so that the fresh glucose smoothly and undisturbingly arrives to every neuron in need.
Band-aid and a kiss in the forehead
If a new axon, together with a new synapse is born (when we gain experience or new insight), first support they get is from astrocytes, guiding them to ther destination. An oligodendrocyte is then stimulated to myelinate the axon, so it can function properly. If, however, an existing nerve gets damaged, a specific form of astrocytes is the first to react. A formation known as the glial scar, which stops the propagation of injury and ensures stability of the surrounding region, can form around injuries happening in the central nervous system. This scar is still the topic of many a debate regarding its usefulness. On one hand, it stops injury propagation and helps the surrounding cells heal faster. But, on the other hand, it has been seen as disruptive for new neuron development. To put it into perspective, let us imagine a back injury, where the spinal cord has been disrupted. Blood vessels burst and axons snap in half, severing the influx of information from below the injury point. In matter of seconds, as the immune system weaves its protective layer from outside the spinal cord, so do the astrocytes from the inside. Any bleeding and loss of material is stopped as the first order of business, then reactive astrocytes band together and protect the injured site. Depending on the severity and position of the injury, a glial scar can form, halting the spread of injury, but also hindering neural regeneration. Any bleeding and loss of material is stopped as the first order of business, then reactive astrocytes band together and protect the injured site. Depending on the severity and position of the injury, a glial scar can form, halting the spread of injury, but also hindering neural regeneration. Any bleeding and loss of material is stopped as the first order of business, then reactive astrocytes band together and protect the injured site. Depending on the severity and position of the injury, a glial scar can form, halting the spread of injury, but also hindering neural regeneration.
Dichtiomy of central nervous system injury. Credit: Kyushu university
If the glial scar forms, the injury site heals faster, but can be left without axons, halting all further communication. If the glial scar is absent, the injury site has a much higher chance of axonal growth, but the injury can persist for much longer, potentially crossing from acute into chronic injury.
Astrocytes are still poorly understood and not enough researched. The many benefits they provide also cause many disorders and diseases that are still untreatable, or even mislabled. Evolutionary comparison shows that their introduction to the central nervous system boosts cognition and complexity of organisms, and humans would certainly not be the same were it not for brains' janitors!
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