Astrocytes in CNS

Astrocytes is one of the most abundant glial cells that reside in the Central Nervous System (CNS). They carry indispensable supportive functions. What are their main functions?

Posted by Gnefil Voltexy on 2022-03-19
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What are the main functions of astrocytes in the CNS?

Astrocytes?

Astrocytes are a kind of neuroglia in the Central Nervous System (CNS), they are part of macroglia classification and have an ectodermal, neuroepithelial origin. Astrocytes provide the supportive function on all levels of nervous tissue organization in CNS including homeostasis and defence of CNS (Verkhratsky and Nedergaard 2018). The functions that astrocytes carry out are as diverse as their morphological heterogeneousness, it is not possible to cover such a wide topic fully in this discussion, though it is worthy to mention some of the main functions they support.

Shaping the CNS

First, astrocytes have a role in the developmental process of CNS. It helps regulate the cellular fate to neurogenesis or gliogenesis, depending on the needs of the CNS at each stage. In embryonic neuronal development, the radial glial cells not only produce astrocytes as required but also part of them form radial astrocytes for future adult neurogenesis. Astrocytes have a huge impact on synaptogenesis and correct synaptic transmission. As soon as in early development when the nervous system is overloaded with synapses, astrocytes mark those unnecessary synapses with molecular markers so that microglial cells can phagocyte them (Kettenmann, Kirchhoff and Verkhratsky 2013). Now, nearly half of the synapses would not be able to form if astrocytes were not there, they work on synaptic formation, maturation, maintenance, and synaptic elimination. Astrocytes surround each synapse with their long and thin processes, forming what is called an astroglial perisynaptic sheath, to isolate functionally each synapse with their neighbours, as they do not want the neurotransmitters of one to interfere with another (Verkhratsky and Nedergaard 2014). Microglial processes can inspect the synapses, as part of neuronal-astroglial-microglial networking.

Net of “blood canal”

Moreover, astrocytes contribute to the structural formation of CNS. They raise scaffold to the functional architecture in the grey matter by forming individual astroglial domains. Astroglial domains are neuronal-glial-vascular units built around a neuronal network, in this way, astrocytes can help regulate further the microcirculation in each sub-neural environment in detail. Also, glial-vascular interfaces are used in the Blood-Brain Barrier (BBB). CNS is a highly important and vulnerable system in the body, so, to prevent highly dangerous substances and possible toxins from regular blood vessels, the brain needs to exhaustively examine all the substances that are passed to the brain. The separation of regular blood from the brain is achieved by BBB. Astrocytes’ glial-vascular interface controls over the tight junction that on the one hand impedes all substances pass from BBB, and on the other hand actively transports substances from BBB that are needed (Verkhratsky and Butt 2007). In some animals, like Elasmobranchii, astrocytes form part of the tight junction. When inside the brain, astrocytes cover completely the brain vessels and capillaries with the perivascular processes, maintaining organ homeostasis.

Environmental maintenance

Astrocytes have remarkable metabolic homeostasis. As the only cells capable of controlling water flux inside CNS, astrocytes regulate the microenvironment of the synapses and neurons with their aquaporins (Verkhratsky and Butt 2007). Because of this characteristic, they are in charge also in the glymphatic system inside CNS. Neurons often create wastes, degraded protein during their life and metabolism, which require astrocytes to transport and clean up. All blood vessels in BBB are wrapped by endothelial tight junction in CNS, then covered by a layer of vascular base membrane and astrocyte vascular endfeet. The space in between, the perivascular space, is filled with extracellular fluid, the cerebrospinal fluid. This entire flow enters through the para-arterial space as an influx with nutrients and other substances. Then the astrocytes drain the water from the para-arterial space with their water channels. Once supplied with water, they clean and washes neurons debris through connective flow. The wastes are transported and end at the outflux flow of the vessels, the para-venous efflux. And finally, this fluid is eventually cleaned out from the brain.

Energy depository of neurons

Another important metabolic function of the astrocytes is that they are the supplier of energies for neurons when necessary. Even though the brain only has around 2% of the body mass, it consumes at least 20% of the total energy gained and takes around 10% of the cardiac blood output. This big amount of energy is normally split in half, for neurons and astrocytes. Neurons normally consume the energy directly as soon as they arrive in 90%-95%, in which its major part is used on synapse and to maintain Sodium-Potassium pump (Magistretti 2015). In contrast, astrocytes do not consume most of the energy, they store most of the glycogen for supply neurons in the future. In the case of a neuron synapse using glutamate, astrocytes would receive the synapse signal by glutamate receptors. This signals the astrocytes to activate glycolysis, and as result, lactate is produced, which is then transported to neighbouring neurons to provide extra energy (Dringen, Gebhart and Hamprecht 1993).

Chemical homeostasis

In addition, astrocytes regulate systemic homeostasis with chemosensing. It can sense the sodium in the blood vessels like a “salt sensor”, by Nax, a concentration-gated sodium channel. An increase in sodium in CNS will increase activate this channel to stimuli and increase the lactate production in astrocytes, and this signals GABA neurons so that they control the efflux quantity of sodium in the blood. Also, they chemically sense the CO2 concentration in blood vessels. If the concentration is too high, it activates calcium waves inside astrocytes which causes ATP release and signals respiratory neurons to enhance ventilation.

Furthermore, a key role of astrocytes is to control the CNS microenvironment with chemical homeostasis. When neurons start to be active, they cause changes in local supply flow because more blood and water is needed, known as functional hyperaemia. Astrocytes are there to control this flow by regulating neurovascular volume. Also, astrocytes actively participate in molecule pick up to maintain local concentrations, for example, potassium buffering. When extracellular potassium concentration exceeds the limits, astrocytes collect the extra potassium to balance intracellular and extracellular proportions. These potassium ions will be transported to neurons later. Another essential mechanism to maintain synapses as mentioned earlier is the neurotransmitters recollection in the synaptic valley. After a synapse between neurons, astrocytes pick up the glutamate or GABA left in the synaptic space, turn them into glutamine and return them to neurons. This is a necessary process for neurons as they cannot create glutamate or GABA by themselves.

Astrocytes cover a huge variety of supportive functions in CNS, they are the indispensable stewards of neurons. As imperative supportive cells, astrocytes are not less important for not firing action potentials, without their support, CNS cannot exist (Verkhratsky and Nedergaard 2018).

References:

  • Dringen, R., Gebhardt, R., and Hamprecht, B. (1993) “Glycogen in astrocytes: possible function as lactate supply for neighboring cells”, Brain research, 623(2), pp. 208-214.
  • Kettenmann, H., Kirchhoff, F., and Verkhratsky, A. (2013). “Microglia: new roles for the synaptic stripper”, Neuron, 77(1), pp. 10-18.
  • Magistretti, P.J., and Allaman, I. (2015) “A cellular perspective on brain energy metabolism and functional imaging”, Neuron, 86(4), pp. 883-901.
  • Verkhratsky, A., and Butt, A. (2007) “Glial neurobiology: a textbook”. John Wiley & Sons, pp. 93-123.
  • Verkhratsky, A., and Nedergaard, M. (2014) “Astroglial cradle in the life of the synapse”, Philosophical Transactions of the Royal Society B: Biological Sciences, 369(1654), 20130595.
  • Verkhratsky, A., and Nedergaard, M. (2018) “Physiology of astroglia”, Physiological reviews, 98(1), pp. 239-389.