I Can’t Believe It’s Not Glue!

When we hear the words “brain cells” most of us immediately picture the spindly, spider-like neurons that send electrical messages through our brain. But did you know that these make up just 10% of our brains? The other 90% is comprised of cells called glia, Greek for “glue”. For many years, glia were quite literally thought to be the ‘glue’ of the brain, supporting the all-important neurons. We observed that neurons could send electrical signals, whereas glia could not, turning our scientific attention toward neurons as the active, information processing components of the nervous system. In the last twenty-or-so years, however, it has become clear that glia are far more than cerebral superglue. They are now thought to play a key role in how our brains work and process information, both in health and disease[1, 2].

Glia can be divided into two categories: microglia are like the immune cells of the brain, vacuuming debris and foreign bodies; macroglia come in several flavours, and the most important of these for information processing are the astrocytes – star-shaped cells found throughout the brain.

Astrocytes have a well-characterised support role. They control the composition of the soupy solution that surrounds the neurons, for example by controlling potassium ion concentration. They also help clear away the chemical transmitters which neurons release to communicate with each other. Their role in these simple tasks has begun to receive widespread attention in recent years, and is central to how our brains functions. For example, by controlling how quickly chemical transmitter is cleared from neuronal junctions, astrocytes can shape the messages that neurons send to each other, making them longer, shorter, widespread or targeted.

Furthermore, astrocytes are play active roles in brain signalling. Like neurons, they can receive, process and send signals, and express many of the same chemical receptors that enable them to receive chemical messages. Although they can’t send electrical signals, they can communicate with each other via a different method, using local changes in calcium concentration that spread throughout the cell and often into neighbouring cells. They can even release chemical transmitters, including ATP, serine and glutamate, which signal back to neurons. It thus appears that glia are just as capable in all brain signalling functions.  But do they really do this in a living, signalling, behaving brain?

This question has raised much controversy. Whilst it has become clear that glia can send messages, some scientists debate that this is only a property they exhibit in a petri dish, and may not be important in real life. It is is still, nevertheless, an important area of research as we continue to discover the unknown capabilities of glia. One group of scientists have shown that inhibiting the glia in the region of the brain that controls breathing disrupts the regular, cyclical activity of this network[3]. As we begin to see how glia can alter and contribute to signalling in the brain, a new layer of complexity is being added to the baffling world of neuroscience.

However, the functions of glia are not purely positive. Malfunctions in glial signalling are starting to be implicated in a number of diseases. Take spinal cord injury, which is devastating and often results in untreatable paralysis. This is largely because neurons in our spinal cord cannot re-grow once broken, leaving lower limbs without connections to the brain. Glia, not neurons, are responsible for this outcome. Following an injury the local glia react, multiplying to form a physical scar. They also release chemicals that inhibit neuronal re-growth. It has been shown that if you kill off the glia following spinal injury in animals, neurons grow back and connect to cells below the injury[4]. However, glia serve in important purpose: they stop neurons growing excessively and making aberrant connections. Reducing or controlling the glia, and doing so safely (i.e. without abnormal connections forming), is an important and active area of research for spinal cord injury.

The signalling function of astrocytes can also go wrong. Such dysfunction is beginning to be implicated in epilepsy, a disease in which an imbalance of excitation and inhibition in the brain causes seizures. It can result from dysregulation of chemicals in the brain, including potassium and glutamate, both of which are controlled by astrocytes. Indeed, several studies have found that brain samples from epileptic patients have altered levels of glutamate metabolism in glia[5], and blocking glutamate transporters in animals can induce seizures[6].

Over the last few decades glia have had their status rapidly lifted from simple “glue” to active and important signalling cells in the brain. Twenty years ago neuroscientists probably thought the dynamic and interconnected networks of the brain couldn’t get more complicated. Whilst this new layer of complexity isn’t making neuroscience any easier to grasp, it has certainly made it more intriguing.

1.  Fellin, T., Communication between neurons and astrocytes: relevance to the modulation of synaptic and network activity. Journal of Neurochemistry, 2009. 108(3): p. 533-544.
2. Araque, A. and M. Navarrete, Glial cells in neuronal network function. Philos Trans R Soc Lond B Biol Sci., 2011. 365(1551): p. 2375-2381.
3. Hülsmann, S., et al., Metabolic coupling between glia and neurons is necessary for maintaining respiratory activity in transverse medullary slices of neonatal mouse. European Journal of Neuroscience, 2000. 12(3): p. 856-862.
4. Moon, L.D.F., et al., Robust Regeneration of CNS Axons through a Track Depleted of CNS Glia. Experimental Neurology, 2000. 161(1): p. 49-66.
5. Eid, T., et al., Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. The Lancet, 2004. 363(9402): p. 28-37.
6. Demarque, M., et al., Glutamate Transporters Prevent the Generation of Seizures in the Developing Rat Neocortex. The Journal of Neuroscience, 2004. 24(13): p. 3289-3294.