Brain activity intensity drives need for sleep

September 16, 2019

Science Daily/University College London

The intensity of brain activity during the day, notwithstanding how long we've been awake, appears to increase our need for sleep, according to a new UCL study in zebrafish.

The research, published in Neuron, found a gene that responds to brain activity in order to coordinate the need for sleep. It helps shed new light on how sleep is regulated in the brain.

"There are two systems regulating sleep: the circadian and homeostatic systems. We understand the circadian system pretty well -- our built-in 24-hour clock that times our biological rhythms, including sleep cycles, and we know where in the brain this rhythm is generated," explained lead author Dr Jason Rihel (UCL Cell & Developmental Biology).

"But the homeostatic system, which causes us to feel increasingly tired after a very long day or sleepless night, is not well understood. What we've found is that it appears to be driven not just by how long you've been awake for, but how intensive your brain activity has been since you last slept."

To understand what processes in the brain drive homeostatic sleep regulation -- independent of time of day -- the research team studied zebrafish larvae.

Zebrafish are commonly used in biomedical research, partly due to their near-transparent bodies that facilitate imaging, in addition to similarities to humans such as sleeping every night.

The researchers facilitated an increase in brain activity of the zebrafish using various stimulants including caffeine.

Those zebrafish which had drug-induced increased brain activity slept for longer after the drugs had worn off, confirming that the increase in brain activity contributed to a greater need for sleep.

The researchers found that one specific area of the zebrafish brain was central to the effect on sleep pressure: a brain area that is comparable to a human brain area found in the hypothalamus, known to be active during sleep. In the zebrafish brain area, one specific brain signalling molecule called galanin was particularly active during recovery sleep, but did not play as big a role in regular overnight sleep.

To confirm that the drug-induced findings were relevant to actual sleep deprivation, the researchers conducted a test where they kept the young zebrafish awake all night on a 'treadmill' where the fish were shown moving stripes -- by imitating fast-flowing water, this gives the fish the impression that they need to keep swimming. The zebrafish that were kept awake slept more the next day, and their brains showed an increase in galanin activity during recovery sleep.

The findings suggest that galanin neurons may be tracking total brain activity, but further research is needed to clarify how they detect what's going on across the whole brain.

The researchers say their finding that excess brain activity can increase the need for sleep might explain why people often feel exhausted after a seizure.

"Our findings may also shed light on how some animals can avoid sleep under certain conditions such as starvation or mating season -- it may be that their brains are able to minimise brain activity to limit the need for sleep," said the study's first author, Dr Sabine Reichert (UCL Cell & Developmental Biology).

The researchers say that by discovering a gene that plays a central role in homeostatic sleep regulation, their findings may help to understand sleep disorders and conditions that impair sleep, such as Alzheimer's disease.

"We may have identified a good drug target for sleep disorders, as it may be possible to develop therapies that act on galanin," added Dr Reichert.

https://www.sciencedaily.com/releases/2019/09/190916110556.htm

Sleep disorder linked with changes to brain structure typical of dementia

July 4, 2018

Science Daily/European Lung Foundation

Obstructive sleep apnea is associated with changes to the structure of the brain that are also seen in the early stages of dementia, according to a new study.

OSA, where the walls of the throat relax and narrow during sleep stopping breathing, is known to reduce levels of oxygen in the blood. The new study suggests that this drop in oxygen may be linked to a shrinking of the brain's temporal lobes and a corresponding decline in memory.

The researchers say the study provides evidence that screening older people for OSA and giving treatment where needed could help prevent dementia in this population.

The study was led by Professor Sharon Naismith from the University of Sydney, Australia. She said: "Between 30 and 50% of the risk for dementia is due to modifiable factors, such as depression, high blood pressure, obesity and smoking. In recent years, researchers have recognised that various sleep disturbances are also risk factors for dementia. We wanted to look specifically at obstructive sleep apnoea and its effects on the brain and cognitive abilities."

The researchers worked with a group of 83 people, aged between 51 and 88 years, who had visited their doctor with concerns over their memory or mood but had no OSA diagnosis. Each participant was assessed for their memory skills and symptoms of depression, and each was given an MRI scan to measure the dimensions of different areas of the brain.

Participants also attended a sleep clinic where they were monitored overnight for signs of OSA using polysomnography. This technique records brain activity, levels of oxygen in the blood, heart rate, breathing and movements.

The researchers found that patients who had low levels of oxygen in their blood while they were sleeping tended to have reduced thickness in the left and right temporal lobes of the brain. These are regions known to be important in memory and affected in dementia.

They also found that this alteration in the brain was linked with participant's poorer ability to learn new information. The researchers say this is the first time a direct link of this kind has been shown.

Conversely, patients with signs of OSA were also more likely to have increased thickness in other regions of the brain, which the researchers say could be signs of the brain reacting to lower levels of oxygen with swelling and inflammation.

OSA is more common in older people and has already been linked with heart disease, stroke and cancer, but it can be treated with a continuous positive airway pressure (CPAP) device, which prevents the airway closing during sleep.

Professor Naismith added: "We chose to study this group because they are older and considered at risk of dementia. Our results suggest that we should be screening for OSA in older people. We should also be asking older patients attending sleep clinics about their memory and thinking skills, and carrying out tests where necessary.

"There is no cure for dementia so early intervention is key. On the other hand, we do have an effective treatment for OSA. This research shows that diagnosing and treating OSA could be an opportunity to prevent cognitive decline before it's too late."

Professor Naismith and her team are now working on research to find out whether CPAP treatment can prevent further cognitive decline and improve brain connectivity in patients with mild cognitive impairment.

Andrea Aliverti, Professor of Bioengineering at Politecnico di Milano, Italy, is Head of the European Respiratory Society's Assembly on Clinical Physiology and Sleep and was not involved in the research. He said: "We already know that as well as disrupting sleep, OSA can increase the risk of high blood pressure, type 2 diabetes, heart attack and stroke. This research adds to evidence that OSA is also linked to dementia and suggests a likely mechanism for the link. However, we can treat OSA and measures such as stopping smoking and losing weight can reduce the risk of developing the condition."

https://www.sciencedaily.com/releases/2018/07/180704194350.htm