Glial Cells Are as Vital as Neurons for Brain Function

Neurons are the most well-known cells in the brain but they are not the only type of cell in this organ. The other main type is the glial cells, also known as neuroglia.

Glia comes from the Greek word for glue, reflecting the view of these cells when they were first characterised as being merely a structural support for neurons in the brain. But further research showed that a class of neuroglia called oligodendrocytes supply nutrients to the neurons, and generate the myelin sheath that wraps such cells. Neuroglia have generally been considered very much secondary to neurons in terms of importance. Recently though, that view has been changing, for it turns out that glial cells can play a highly active role in brain cell communication, and perhaps in the development of human intelligence.

One reason why neuroglia were underestimated for so long was that they seemed to have no way of transmitting information in the brain. Neurons carry information via the "action potential," an electrical signal, and communicate with other neurons by releasing chemical messengers across connecting synapses. In contrast, neuroglia cannot generate action potentials. However, recent studies have shown that chemical communication is just as important for them. They have many of the same cell surface receptors as neurons, allowing them to communicate with both neurons and other neuroglia.

Astrocytes

One class of neuroglia, called astrocytes, play an important role in the formation of synapses. If rodent neurons are cultured outside the body in the absence of astrocytes, they form few synaptic connections. But if astrocytes are added to the culture, the number of synapses, and synaptic activity, rapidly rises. Astrocytes secrete chemicals that enhance synapse formation and directly regulate synaptic activity. The close physical association between synapses and astrocytes ensures that these are the first cells to respond to changes in synaptic activity during embryo development, but also in the adult brain. Astrocytes are highly dynamic, constantly modulating their association with synapses — and thereby their influence — the dynamic pattern being dependent on the state of the brain.

Microglia

Another class of glial cells called microglia make up about 10 percent of the cells in the brain. For some years now, these cells have been recognised as the brain’s primary defenders against disease; they identify injured neurons and destroy them, and strip away defective synapses, thereby removing diseased cells that have a negative impact on the rest of the brain. For decades, scientists thought of microglia only as immune cells and believed that they were quiet and passive in the absence of an infectious invader.

Recently though, that idea has begun to change. One clue that microglia might have a wider role was the discovery that these are the fastest moving cells in a healthy brain. For instance, recent studies have revealed that microglia can reach out to surrounding neurons and contact synapses in the absence of disease. These cells regulate the number of synaptic connections just as a gardener prunes a plant. This is important because, for reasons that are not fully understood, the brain begins with more synapses than it needs. Cornelius Gross of the European Molecular Biology Laboratory in Heidelberg, who studies this process, has shown that microglia help sculpt the brain by eliminating unwanted synapses. But how do the microglia know which synapses to remove and which to leave?

In fact, microglia can receive two types of messages from neurons — one that identifies synapses that play an important role and should be preserved, and another that highlights weaker ones that need pruning. Pruning is important since Gross’s team has shown that removing the receptor for a chemical named fractalkine from microglia leads to weak synaptic contacts caused by defective synaptic pruning in the hippocampus, a brain region involved in learning and memory. Gross believes this shows that during embryo development, neurons "call out" to microglia for assistance with pruning.

Yet there are also mechanisms in the brain to avoid over-pruning. Another study by Emily Lehrman and Beth Stevens of Boston’s Children’s Hospital showed that useful synapses not destined to be pruned are identified by a protective protein "tag" that deters microglia. If the receptor is eliminated genetically in a mouse, synapses are no longer protected, leading to excess engulfment by microglia and over-pruning of neuronal connections.

Glial cell function in humans vs. other species

Recent studies of the role of glial cells in the brain are also revealing potentially important differences between humans and other species in the functions of these cells. They have shown that astrocytes reach dramatically longer distances in the human brain and propagate chemical signals faster than astrocytes in other species. These features suggest an amplified role for human astrocytes in brain function. Other studies have shown that the genes that are switched on or off in human astrocytes are quite different from those in mice, so astrocytes may have evolved to play quite different roles in the two species.

Intriguingly, Steven Goldman and colleagues at the University of Rochester in New York have recently shown that baby mice whose brains were injected with human astrocyte precursor cells grew up to have better memories and learning abilities than their normal counterparts. This suggests that human astrocytes may have an enhanced ability to control synapses. But future studies injecting chimpanzee or macaque glia into the mouse brain will be needed to determine whether the effects are due to properties unique to the human cells or ones that are common to those of all primates.

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Implications of glial cell abnormalities

Another hint concerning the functions of astrocytes comes from studies of autism. Many genes implicated in some types of autism are expressed in astrocytes. Moreover, when researchers examined astrocytes in frontal brain regions in postmortem samples from some individuals who had been diagnosed with autism, they found the astrocytes to be denser, with smaller cell bodies and fewer and shorter projections, than in unaffected individuals. Changes in glial cells have also been claimed to play a role in dyslexia, stuttering, tone-deafness, chronic pain, epilepsy, sleep disorders, and even pathological lying.