Neutrinos and Nutrition

A way to boost the effectiveness of radiotherapy and protect patients and even astronauts from the effects of radiation exposure has been discovered by scientists at Oslo University.

Radiotherapy causes side effects because the dose of radiation needed to destroy sufficient numbers of cancers cells also causes significant damage to healthy tissue. But the dose cannot be reduced or delivered in smaller amounts over time because radiation exposure also causes and effect called "radiation resistance" in the surviving cells, whereby subsequent doses of radiation are much less effective.

But now Erik Pettersen and Nina Edin at Oslo University have discovered the chemical basis of this resistance effect, meaning that if it can be selectively deactivated in cancer cells, or conversely boosted in healthy tissue, then the side effects of radiotherapy could be minimised by cutting down the dose.

They made the discovery by showing that growth medium from cells exposed to radiation can confer radio-resistance upon second batch of non-irradiated cells. This was the initial proof that a chemical signal of some kind must be being secreted by radiation-exposed cells. In the context of a human body exposed to radiation, this means that, paradoxically, radiation-exposed healthy tissue can also end up protecting the cancer cells by secreting the same signals.

Now they've identified the factor responsible, a signal called TGF-beta-3, which locks cells into a resistant state. Removing it from a tumour renders it vulnerable again, whilst elevating the signal in healthy tissue can lead to protection.

The potential benefits don't stop there though. As the researchers point out, the same trick could be exploited to protect humans from incidental radiation exposure - such as astronauts and high-altitude fliers - as well as patients undergoing high-dose x-ray investigations like CT scans...

Chris - Dr. Denis Burdakov is a Neuroscientist and he's been looking at how the brain ensures that we eat a balanced diet.  Denis, welcome.

Denis -   Hello.

Chris -   First of all, why is it important that the brain can register what we're eating?

Denis -   I think it's important for two reasons.  The first of those is that in order to respond to energy deficiencies, sort of to a fall of nutrients in our blood, we need to change our behaviour, we need to change eating behaviour, we need to find food and so on, or stop eating if we are getting too many nutrients. Behaviour is controlled by the brain so that's why it's important for the brain itself to sense the nutrients in the body.

Chris -   But also, not just pile in tons of glucose and nothing else.  In some way, the brain knows what particular micronutrients. Because if you study an animal in its natural environment, it tends to eat a diet that's right for it, arguing there's something behavioural about searching out the right foods that are right for that animal's metabolism.

Denis -   That's correct and it's been quite mysterious how the brain does this because most studies looked at effects of glucose on special brain cells which regulate alertness and food seeking.  Things like how protein components and fat is sensed have been much more elusive in mechanistic terms.

Chris -   So how did you set about trying to answer that then, to work out what the brain is doing to register when I go for dinner, what micronutrients I've consumed?

Denis -   So we were originally motivated by the recent findings that our diet and our sleep patterns are so closely related.  You can kind of mess up your sleep by eating a high fat diet and on the other hand, if you mess up your sleep, if you have a jet lag and so on, you can over consume food and develop obesity and diabetes.  And we're actually working on brain cells that regulate both wakefulness and feeding: they simulate wakefulness and they drive feeding, and we were putting different nutrients on these cells to see whether these cells themselves as well as controlling behaviour can actually measure what nutrient levels we get in the body.

Chris -   In other words, you'd squirt some glucose onto them, some sugar, they might change their activity, but then you could also ask, "Well what happens if I give them a dose of the amino acids, the building blocks of protein for example?"

Denis -   Exactly.  So we started with sugar about 5 years ago and we found out that amazingly, if you increase the concentration of sugar around these brain cells called orexin neurons, then the cells fall silent and they don't emit these impulses anymore, that they drive wakefulness and food seeking.  So more recently, sort of this year, we asked, what about other components of meals?  We don't just eat glucose.  There is always some protein around.  So we mixed together an amino acid mixture based on the egg white composition.  So these proteins in egg white get digested to a certain combination of amino acids, and it's known at what concentrations these amino acids reach the brain.  So we mixed this together and we put them on those wakefulness promoting orexin neurons, and we expected the cells to fall silent because glucose silences them.  But actually, we found that these egg white-like amino acids stimulate these wakefulness promoting neurons.

Chris -   So in other words, they are registering some of the micronutrients that we're eating.  So there are specific cells that are specifically sensitive to some of the things that are coming into the body.

Denis -   Absolutely.  So in the brain region called the hypothalamus, there are several populations of cells that can sense nutrients selectively but the new thing that we found is that all nutrients don't do the same things.  Some nutrients can upregulate the activity of these brain cells which stimulate food seeking behaviour, other nutrients can shut them down and we think we now are looking at this population of cells that control the balance between different nutrients in the diet.

Chris -   If you look at amino acids, because they come in two flavours don't they?  They come in the kinds that we can make in the body.  They also come in the other flavour, the kind we can't make in the body, and we have to eat.  And if you become deficient in those, you have metabolic problems.  So are these cells differentially sensitive to those different flavours, for want of a better word, of amino acids?

Denis -   They seem to be extremely differential to the two groups of amino acids.  So the essential amino acids, the amino acids you cannot make and you need to consume, these cells effectively do not see, but the non-essential amino acids are potent stimuli of these cells that drive feeding.  So we think - the point of this is that if you consume a meal which is unbalanced then it has too many amino acids that you can make in the body and you don't really need, these cells will make you keep eating until you find and consume essential amino acids thereby providing the body what it really needs.

Chris -   Does this shed any light on the claim that if you want to not end up hungry again by 11 o'clock in the morning, eat a big fried breakfast that has got loads of protein in it.  You know, the bacon and the eggs actually help to stave off hunger for longer.  Does it help us to understand why that might be true?

Denis -   Well actually, it's almost the opposite for what you'd expect.  You think if you eat a lot of proteins, especially proteins which are non-essential amino acids, you would actually - you might get hungrier quicker, but you also feel more alert.  So, these cells will make you more alert, possibly more efficient at work if you eat a protein rich breakfast.  Another thing these cells do apart from driving feeding, they actually tell the body to burn calories through thermogenesis and so on.  So the net effect on calories is actually negative.  So they tell you to burn more calories than the calories you consume.  So these cells will kind of - they might make you hungry, but they will make you more alert and they would actually keep your body weight down overall.

Chris -   so to finish off Denis, if we could target these neurons then in people who have a tendency to overeat, we can make them burn more energy but maybe also, eat less in the first place so their weight would come down for two reasons.

Denis -   Well, absolutely.  That's the exciting thing.  Possibly, we could find a dietary combination of nutrients which can tune the cells and control body weight as well as alertness, and that's what we're working on right now.

Chris -   Super!  We'll leave it there for a second.  That's Denis Burdakov.  He's from Cambridge University.  He published the work he's just been talking to about in the journal Neuron this week.