gliaclub-blog

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Better understanding dementia, part I

The next few posts I would like to dedicate to just one disease: Alzheimer’s Disease. This area of research is slowly gaining more interest, both scientifically and publically and is only one example of neurodegenerative diseases. The name indicates that in these disorders, neurons slowly degenerate and die, leading to a range of different symptoms. But why discuss this in so much detail? Because these diseases, and Alzheimer’s more specifically as it is the most common, are going to be the next hurdle for our Western societies. As we managed to reduce or eliminate other great health risks, such as smallpox, we get to live longer and grow older. Whilst this has many advantages, it also means that age-related diseases, such as Alzheimer’s, are getting more and more common. 47 million people are currently believed to live with this horrific disease and this number is predicted to double every 20 years (according to the World Alzheimer Report 2015).

Next to dementia, or amnesia, the other lesser known symptoms of this disease are anomia, the inability to name objects, apraxia, problems with specific movements or even speech, agnosia, problems to recognize familiar objects and aphasia, problems with speech. Another category of symptoms is summarized under “associated features”, which can include sleep problems, anxiety or depression. Research is slowly catching up to the sad reality of this disease we are facing, trying to answer the many questions about this disease: Why does it affect some but not others? What is exactly happening in the brain and which pathways are involved? Personally, I am interested in answering as many of these questions as possible, having made it the focus of my research.

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Implanting neurons into the brain

This is a really interesting paper recently published by a group in Japan. In Parkinson’s disease, neurons degenerate and die, leading to severe symptoms, including tremor and inability to move. One approach to treat this rather complicated disease is to, quite simply put, implant new neurons into the brain area with the highest damage to make up for the dying neurons. Acquiring neurons to implant into the brain however is difficult, because accessing them in the brain requires an invasive surgery and once they’re removed, these primary neurons won’t live in vitro, in the lab, for much longer. So instead, these researchers used induced pluripotent stem-cells. Stem cells are cells, which can become any kind of cell, for example the initial cells in an embryo. Again, access to embryonic stem cells is limited, also because of ethical issues, so that’s where the word “induced” comes in. In 2006, researchers in Kyoto found a way of “re-programming” any cells to make them become stem-cell like cells. Particularly for the neuroscientific field this was a big breakthrough, as it is now possible to take skin samples from patients, make these skin cells into stem cells and then model the embryonic development to differentiate them into neurons. This paper takes it a step further: They showed that when injected into the brain of monkeys, the reprogrammed neurons can integrate into the existing network and actually improve some motor functions in this disease model. It will be a while until this can be applied in human, requiring many more tests and trials, but it is a first exciting step and definitely highlight the use of using induced stem cells as a model.

http://www.nature.com/nature/journal/v548/n7669/full/nature23664.html

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The glia club: Supporting the grey matter of the brain

Neurons are viewed as the main heroes of the brain, encoding information communicating with each other, which can lead to memories, brilliant thoughts and consciousness. But there are other cells within the brain and they are the secret helpers of the brain and mind: glia cells. So what can be as, or even more important, than the signal transduction of neurons?

Oligodendrocytes are the one of three subtypes of glia cells and when they fail and die, a well-known disease ensues: Multiple Sclerosis (MS). Neurons transmit information in the form of electrical signals down their axon, an elongated part of their cell which can stretch all the way from the foot to the spinal cord, and in the majority of neurons the axon is “insulated” by oligodendrocytes. This means, that electricity can speed down faster the axon and so information transmission is quicker. Oligodendrocytes wrap around the neurons in the form of myelin sheets and when these sheets degenerate in MS, signal transduction is slowed down and impairments ensure.

The star-like shaped cells, astrocytes, are another form of glia cells. They do a lot of different things within the brain such as being closely associated with the blood brain barrier, which prevents harmful molecules from entering the brain, and transport nutrients to neurons. Astrocytes also help neurons stay healthy through informing them of nearby inflammation and prevent toxic overstimulation of neurons by removing neurotransmitters from the environment. Intriguingly, astrocytes also seem to communicate with each other, through calcium waves, indicating changes within the astrocytes themselves, which spread throughout astrocytes, similar to neuronal activity spreading through the brain, but less understood. Astrocytes seem to be the dark horse of the brain. They are involved in so many processes and perform so many functions, that dysfunctional astrocytes are detrimental to the brain. Studying these dysfunctions on the other hand though is difficult, as understanding why this leads symptoms is a challenge exactly because astrocytes are involved in so many functions.

Finally, there are microglia cells. In the rest of the body, we have immune cells which can detect any foreign intruders and can then alert the body to start killing these cells. Microglia have this function in the brain. They can detect anything, which isn’t supposed to be there and can alert neurons and astrocytes to the pending attack. In the recent years, microglia have been implicated in a range of diseases such as Alzheimer’s disease.

Glia cells perform so many life-sustaining functions within the brain but have the tendency to be overlooked and personally, I believe this is partially because they are difficult to understand and many secrets they hold are yet to be understood. But simply because it is a challenge, we shouldn’t give up, otherwise the field of neuroscience would have never developed the way it has.

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Soo amazing!!!

My latest video! - An introduction to the cerebellum

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The shocking truth behind electrocuting the brain

The evocative image of neuroscientists torturing either animals or even humans with electricity has been around since electroconvulsive therapy (ECT) has been used in the 1940s and 50s to treat homosexuality. There is, perhaps understandably, a lot of prejudice around using electricity in experiments to find out more about the human brain, so let’s de-mystify current uses of brain stimulation:

For ECT, electrodes are applied directly to the scalp and electricity is passed between them. This technique is now reserved for only the most severe cases of treatment resistant depression and despite how barbaric it may seem, it remains the most effective treatment of depression to date with a success rate of roughly 70%. Modern ECT is now performed under anaesthesia, with minimal side effects, but its “little siblings” are continuing to gain popularity in modern neuroscience.

One of the most prevalent is transcranial magnetic stimulation or “TMS”. A hand-held coil creates an electric field with in the brain and so targeted brain regions can be turned on or off. A similar effect can also be achieved by attaching small electrodes directly to the scalp in transcranial direct current stimulation (tDSC).

( Ridding, M. C. & Rothwell, J. C. (2007) Is there a future for therapeutic use of transcranial magnetic stimulation? Nature)

The underlying idea in both techniques is that neurons conduct electrical currents and when electricity is applied, having an effect on these currents and changing them, the neurons fire either less or more. If a whole group of neurons fires less or more, depending on exactly how they get stimulated, the activity of a whole brain area can be changed. This is a quite exciting technique, as we can observe the effects of turning on or off different brain regions, allowing us to produce a “virtual lesion” in healthy subjects. Previously, without this technique, we would have had to wait until a patent turned up with damage to the particular area of interest.

Electricity can also be directly applied in the brain itself, but this requires surgery to insert the electrodes. A common misperception is that stimulating neurons like this could cause pain, but the brain itself cannot feel pain! There are no pain receptors within the brain. As everybody whose hair ever got pulled can testify, the scalp can feel pain, but after the skull has been opened, inserting an electrode into the squishy grey matter which lays in front of you does not hurt. Again, an electrode in the brain can change the firing rate of neurons and can have incredible results: Shaking and inability to move are signs of Parkinson’s disease and here, implanting electrodes into a specific brain region can significantly reduce these symptoms.

Why and how this exactly works is not understood yet, like many things when it comes to neuroscience and this leads me to my final point on brain stimulation: it can be an incredible (and as I know from own personal experience mostly pain-free tool) but the results from it are still highly debated within the scientific community. In which specific areas is actually neuronal activity changed? With one area shut down, how could this influence other connected regions? These questions still require answers and some of those answers can only be found with participants, volunteering to receive some sort of brain stimulation, and for this, the technique of brain stimulation has to be understood in the wider population first.