The Many Emerging Roles of Astrocytes

Astrocytes, the star-shaped glial cells in the brain, were long believed to play only supportive roles to the electrically active neurons involved in information processing in the brain. The past few decades, however, have seen an explosion of interest in and research on these cells. Scientists have unearthed an increasing number of functions for astrocytes in neural signalling. It has become clear that astrocytes were grossly underestimated in their size, capabilities, and complexity. Given this, is it possible that astrocytes not only support neural signalling, but themselves play a distinct and active role in the information processing of the brain?

Astrocytes are not electrically active in the classic way that neurons are. They were, therefore, long assumed not to play any active roles in neural signalling. However, experimental methods that allowed for the measurement of calcium release from cells, demonstrated that astrocytes communicated, not through electricity and voltage, but through calcium signalling. Calcium is involved in, but not necessarily responsible for neural signalling. By altering the calcium concentrations around a cell, the astrocytes can influence, but not initiate neural signalling. It could change the likelihood of a neuron firing, the speed at which a neuron could fire, or the size and strength of a connection between two neurons. Calcium, therefore, can add a level of sophistication in signalling to the otherwise binary code of neural processing.

In addition to playing complex roles in the brain, scientists grossly underestimated their size and reach. For many years, scientists used GFAP (glial fibrillary acidic protein), a protein known to be found on astrocytes, in order to view them under a microscope. Using GFAP, astrocytes look like stars: a cell body with processes extending into points. However, over the past decade, scientists began looking at astrocytes by injecting a dye into the cell that would stain the entire cell from the inside. These experiments showed that these initial GFAP-labelled processes actually branch into ever smaller processes, extending across a much greater area than previously seen. Astonishingly, GFAP had been labelling a mere 15% of the entire cell. The sheer extent of these cells is impressive. A single astrocyte in the human brain may have connections with as many as two million neurons. Their processes extend to every corner of the brain and spinal cord.

Astrocytes play a number of important roles in the developing, healthy, and diseased brain. They are involved in cerebral blood flow and metabolism, water transport, act as neural stem cells in neural development, and respond to damage in the brain. In addition, an increasing  number of functions for astrocytes in signalling and information processing have been proposed. Some of these new roles, such as the ability of astrocytes to release neurotransmitters, just like neurons, remain controversial. However, the sheer size and complexity of these cells suggests astrocytes form a sophisticated and interconnected network across the entire brain.

The human brain is significantly more complex than any other animal’s. And yet, other than increasing in number, neurons remain relatively similar across species, regardless of cognitive ability. Astrocytes, on the other hand, become larger, more complex, and more diverse in addition to more numerous as species go up the evolutionary chain. Could these long-underestimated cells be responsible for the complex cognitive tasks that separate the human brain from other animals?

References

Hamilton, N., & Attwell, D. (2010). Do astrocytes really exocytose neurotransmitters? Nature Reviews Neuroscience, 11 (4), 227-238 DOI: 10.1038/nrn2803

Freeman, M. (2010). Specification and Morphogenesis of Astrocytes Science, 330 (6005), 774-778 DOI: 10.1126/science.1190928

Giaume, C., Koulakoff, A., Roux, L., Holcman, D., & Rouach, N. (2010). Astroglial networks: a step further in neuroglial and gliovascular interactions Nature Reviews Neuroscience, 11 (2), 87-99 DOI: 10.1038/nrn2757

Nag S (2011). Morphology and properties of astrocytes. Methods in molecular biology (Clifton, N.J.), 686, 69-100 PMID: 21082367

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