Sleep deficit without the disasters

‘What constitutes a lack of sleep? That's a good question’, says UG neuroscientist Robbert Havekes (38). ‘If you need an alarm to wake up, you could say that you're not getting enough sleep. Or if you really need coffee to get you through the day. A sleep deficit means that you aren't functioning to the best of your ability. If you look at past major disasters, from the explosion of the Challenger to the melt-down in the nuclear power station at Chernobyl, the disaster with the Exxon Valdez oil tanker off the coast of Alaska, the Bhopal gas tragedy and various airplane crashes: they can all be put down to a lack of sleep.’ Although it can’t be classed as a disaster, the fact that general lack of sleep is costing the economy an annual 1.5 to 3% of the GNP in the shape of reduced productivity, increased mistakes and higher absenteeism (as the American RAND Cooperation concluded this spring from an international study) is definitely a cause for concern.

Bad guys

Robbert Havekes became interested in the consequences of sleep deficit during the PhD research he carried out after his degree programme in Behavioural and Neurosciences in Groningen. ‘Peter Meerlo, a sleep expert at the UG, became interested in learning and memory processes, whereas I was a learning and memory expert who became interested in sleep. So we joined forces and are trying to work out what happens to learning and memory processes when people get too little sleep.’ After being awarded a PhD in 2007, Havekes took his Rubicon grant and headed for the University of Pennsylvania to work in the lab of Ted Abel, a leading researcher in the field of the molecular mechanisms behind memory, and how lack of sleep undermines these processes. ‘I thought I'd be there for a year or two, but I stayed for eight’, says Havekes. ‘We tried to get to the bottom of what goes wrong in the brain with a lack of sleep, for example in the hippocampus, a small area of the brain that plays an important role in learning and memory formation. We discovered that when someone doesn’t get enough sleep, specific proteins disturb the connections between brain cells in the hippocampus. By crippling these bad guys in the brains of laboratory animals, we noticed that we could make the memory process resistant to a lack of sleep. The animals were perfectly capable of learning, whether they had slept or been kept awake.’

Drug

Havekes’ ultimate goal is to develop a drug that cancels out the effects of a sleep deficit. ‘Take, for example, shift workers or people who work long shifts in hospitals or restaurants. There are countless situations in which people don't get enough sleep.’ In fact, we're all sleeping less. ‘Over the past sixty years, the average number of hours we sleep has dropped by around one-and-a-half’, says Havekes. ‘In the 1950s, we slept an average of eight hours per night. This has now dropped to six, six-and-a-half hours. This is a big drop, and is obviously related to the current 24-hour economy. We work later, we're available 24/7, want a social life and spend our evenings on the iPad or telephone. The light emitted by the screens on these devices doesn't do our sleep rhythm any good either. In this respect, I don't think we’ll be able to reverse our habit of sleeping less, even knowing just how bad it is for us.’ And a drug isn't even on the horizon yet. ‘At the moment, no-one's saying “just switch off those proteins in my brain”. There's a very delicate balance between strengthening and weakening the connections between brain cells. If this balance is disturbed, which is what happens with a lack of sleep but also in the case of Alzheimer's disease and autism, things start to go wrong and too many connections become disconnected. But you don’t want to cripple the proteins responsible permanently; just suppress them for certain periods.’

International experience

The opportunity that the Rubicon grant gave Havekes to work in a top-class institute abroad was essential to his development as a researcher. ‘I had the chance to learn several totally different techniques, viral techniques, molecular analyses, genetic modification of mice. The Netherlands is a small country, which does fantastic research, but it's always good to see how things are done in another country, another lab, at another, in this case American, institute. I met new people, built up a new network. The knowledge I acquired there is what made me such a catch in Groningen.’ Havekes returned to Groningen in 2015, when he was appointed Assistant Professor in the UG's Groningen Institute for Evolutionary Life Sciences (GELIFES). ‘I saw a lot of potential for expanding neurosciences, whereby I could apply the new techniques I'd learned and answer new questions. I also knew that thanks to the people working in the institute, it was a pleasant, highly motivating working environment. I always enjoyed being there as a PhD student.’ Havekes’ international experience also played a role in the € 1.25 million research grant from the Human Frontiers Science Program, which he and three colleagues from Germany, the United States and South Korea were awarded last March. ‘I worked with the American researcher during my time in the USA’, says Havekes. ‘We came up with the idea of a research project and found two other researchers from different academic fields. This is what Human Frontiers is all about. They want to encourage research at the cutting edge of academic knowledge, and strong interaction between various academic fields.’

Clock genes

Havekes and his fellow-researchers are using the grant to examine what are known as clock genes. These are proteins that regulate our day and night rhythm in the biological clock. ‘These proteins are also found in other brain cells. If you stay awake for a long period, the proteins become more active, but we don't understand exactly why. It's possible that they play a role in the memory loss that occurs when people are deprived of sleep. In this new study, we will try to manipulate the specific proteins, which are important to our biological clock in cells outside, in the hippocampus, for example. This might enable us to identify the clock genes that cause memory problems.’ Is the ultimate outcome of his research that we will never have to sleep again? ‘No, absolutely not’, Havekes is quick to reply. ‘It's not only our brains that need sleep. The other organs in our body need it too. A lack of sleep can cause all kinds of damage: from facilitating cancer and diabetes to high blood pressure and arrhythmia. And memory loss of course.’

Text: Bert Platzer
Source: Broerstraat 5, the alumni magazine of the University of Groningen