an autodidact meets a dilettante…

Here’s the transcript for the next podcast, which I won’t be putting online for another week or so, when I can afford to buy space to host podcasts directly from this site. Then I’ll be able to stick all the fountains podcasts in one place, with the new logo created by a friend of mine, Stuart Rose:

What’s a glial cell?

Today, I’m going to make my first, but hopefully not last, foray into neurobiology. And since neurobiology is about the most complicated subject imaginable, I’ve decided to enter it sideways, so to speak, by looking at glial cells, or neuroglia, as they’re sometimes called. Not that this will make it any easier.

Glial cells – ‘glia’ means glue in Greek – perform a whole range of tasks apart from holding neurons together. They also come in many different varieties, and there’s still a lot we don’t know about them. They make up about half the mass of the brain, and they outnumber neurons many times over, making up between 85% and 90% of brain cells.

Considering the great varieties of roles glial cells play in the central nervous system (CNS), the peripheral nervous system (PNS) and in neurogenesis or the development of the brain, it’s hard to start with a summary or overview. They’re generally a lot smaller than neurons, and the glia/neuron ratio varies greatly between species, with the human brain near the top end. Elephants, though, are much higher with 97% glial cells.

Glial cells emerge from the multipotent precursor cells of the neural crest and neural tube. Radial glial cells act as progenitors and also as scaffolding for the growth and migration of neurons in the brain. They play a role in the development and maintenance of synaptic plasticity in the cerebellum. This function of supporting neurons is typical of all glial cells, with some of them having their own quasi-neuronal tasks. In the vertebrate retina, for example, Muller cells or Muller glia have been found, quite recently, to play a role in the formation of synapses. They’ve also been shown, when the retina is damaged, to re differentiate into progenitor cells which can then become photoreceptor cells.

But I’m galloping forward a bit here. The three main types of glial cells in the CNS are the astrocytes, the oligodendrocytes and the microglia, and some of their functions have long been known, though the detail, as well as a growing number of other roles and functions, are only now being focused on, in what some are describing as a revolution in neurobiology. Dr. Douglas Fields, chief of the Nervous System Development & Plasticity Section of the National Institutes of Health in the USA, argues that our understanding of the brain has been overly influenced by what he calls ‘the neuron doctrine’, that’s to say, a relentless focus on the electrical activity of the brain in the form of action potentials between neurons. The fact that glial cells don’t communicate electrically has meant that their role in brain activity has been largely overlooked for the best part of a century, according to Dr Fields. My layman’s perspective suggests to me that, not being electrical, glial cells just aren’t as flashy or sexy as neurons. ‘I sing the body electric’, Walt Whitman memorably wrote, and maybe he wasn’t thinking about neurons, but he definitely wasn’t thinking about glial cells.

So let’s have a look at some of those glial cell types. Astrocytes – so-called because of their star-like shape and projections – perform lots of functions within the CNS, including providing physical support to neurons through the formation of a matrix, cleaning up chemical debris within the brain, and replenishing chemicals within neurons and so keeping them healthy and well-nourished. This clearly requires communication between neurons and glia. Astrocytes also monitor the fluid surrounding neurons and keep it chemically well maintained. They get rid of the flotsam and jetsam through a process called phagocytosis, which involves engulfing the unwanted particles and essentially digesting them, a process performed by dedicated cells throughout the body.

looks like an astrocyte

Astrocytes nourish the neurons by first obtaining glucose from capillaries, then breaking it down into lactate, the first product of glucose metabolism. The lactate is then released into the fluid surrounding the neurons. The neurons take up this lactate and transport it, as an energy source, to their mitochondria. Astrocytes also maintain a store of glycogen from this process, which may be used in times of high neuronal metabolism.

One of the essential functions of oligodendrocytes is myelination. Now I’m sorry for the polysyllabification there, but I’m talking about the production of myelin sheath, the insulating material that protects the axons of the CNS as well as substantially improving their electrical activity. Myelin is white in colour, and accounts for the white colour of the brain. It’s made up of 80% lipid and 20% protein and it increases, many times over, the strength and efficiency of electrical conduction down the axon. The axon is generally the only part of the neuron sheathed in myelin. The oligodendrocytes are able to sheath as many as 40 axons at once in myelin.

Microglia, the smallest of the glial cells, also engage in phagocytosis to clean up debris, but their most important role is immunological. The brain’s main protection against pathogens is the blood-brain barrier, a layer of endothelial cells similar to the types of cells that line blood vessels and internal organs. When somehow pathogens cross the blood-brain barrier or are introduced into the brain directly, microglia, which are ultra-sensitive to chemical imbalances in the brain, and particularly to extra-cellular potassium levels, move swiftly into action. Microglia perform a similar role in the CNS to that of macrophages in the blood system, but are not as easily replaceable as macrophages, due to the blood-brain barrier. However microglia are extremely plastic which allows them to perform a variety of immunological functions at short notice while also maintaining homeostasis in the brain.

Another type of glia, the Schwann cells, provide support to the nerve cells of the peripheral nervous system (PNS). They wrap themselves around axons, as with oligodendrocytes in the CNS, and in so doing produce myelin, though the process of myelin production is substantially different in the PNS, with one cell producing only one segment of myelin. Schwann cells also clean up debris and play a major role in the regrowth of PNS axons. They arrange themselves into cylinders which guide the tendrils of regenerating axons. When a functioning tendril comes into contact with one of these cylinders it will grow inside it a rate of up to 4mm a day.

There are other types of glia, and the glial cells already mentioned have their subsets and their developmental phases, which all play their part in the development and maintenance of the brain and the nervous systems, yet for a long time neurophysiologists considered the ‘white matter’ of the brain – the glia, predominantly – as passive, with the grey neuronal matter being the active component.

With the renewed interest in glia however, experiments are being conducted that show that when you remove or ablate relevant glial cells, it has a profound effect on an animal’s ability to sense its surroundings. This has been shown in worms and other creatures, and it raises many questions as to how glial cells communicate with neurons in facilitating an effective sense of our environment, without which, we wouldn’t last long.

We now know that the activation of calcium ions provides the principal means of chemical communication between neuroglia and neurons. An increase in calcium ions signals the release of what are now being called gliotransmitters, molecules that travel between cells in a manner similar to neurotransmitters. All this communication has a variety of purposes but it’s the immunological role of neuroglia that has researchers really excited. The neuroglia are able to pick up signals between neurons and respond by controlling neuronal activity, inhibiting or stimulating or refining the action potentials between nerve cells. All of this was completely unsuspected until recently. Their role in such diseases as Parkinson’s, Alzheimer’s, Lou Gehrig’s disease, cancer and AIDS, and even such disorders as OCD (Obsessive-Compulsive Disorder) are now being uncovered through a lot of experimental work. Communication between astrocytes and microglia and neurons are substantially altered in specific ways in each of these diseases. So important have glia become in contemporary neuro-research that there’s talk of ‘the other brain’ or ‘the glial brain’ as opposed to the neural brain. They of course work in tandem, but the point is that we have a lot of catching up to do in researching glia.

It’s worth noting that, though neurons in invertebrate animals are not substantially different from those in vertebrates, glial cells are far less numerous, in proportion to neurons, in invertebrates, where they don’t have the same myelin-producing role. Investigating the increasingly vital and diverse roles played by glia and how they came to evolve in more complex animals will no doubt be a focus of future research.