Sleep switch identified

A switch has been identified that tells the brain it's time to sleep.

The switch in the brain that sends us off to sleep has been identified by researchers at Oxford University's Centre for Neural Circuits and Behaviour in a study in fruit flies.

The switch works by regulating the activity of a handful of sleep-promoting nerve cells, or neurons, in the brain. The neurons fire when we're tired and need sleep, and dampen down when we're fully rested.

'When you're tired, these neurons in the brain shout loud and they send you to sleep,' says Professor Gero Miesenböck of Oxford University, in whose laboratory the new research was performed.

Although the research was carried out in fruit flies, orDrosophila, the scientists say the sleep mechanism is likely to be relevant to humans.

Dr Jeffrey Donlea, one of the lead authors of the study, explains: 'There is a similar group of neurons in a region of the human brain. These neurons are also electrically active during sleep and, like the flies' cells, are the targets of general anaesthetics that put us to sleep. It's therefore likely that a molecular mechanism similar to the one we have discovered in flies also operates in humans.'

The researchers say that pinpointing the sleep switch might help us identify new targets for novel drugs -- potentially to improve treatments for sleep disorders.

But there is much still to find out, and further research could give insight into the big unanswered question of why we need to sleep at all, they say.

'The big question now is to figure out what internal signal the sleep switch responds to,' says Dr Diogo Pimentel of Oxford University, the other lead author of the study. 'What do these sleep-promoting cells monitor while we are awake?

'If we knew what happens in the brain during waking that requires sleep to reset, we might get closer to solving the mystery of why all animals need to sleep.'

The findings are reported in the journal Neuron. The work of the Centre for Neural Circuits and Behaviour is funded by the Wellcome Trust and the Gatsby Charitable Foundation. This study was also supported by the UK Medical Research Council, the US National Institutes of Health, and the Human Frontier Science Program.

The body uses two mechanisms to regulate sleep. One is the body clock, which attunes humans and animals to the 24 hour cycle of day and night. The other mechanism is the sleep 'homeostat': a device in the brain that keeps track of your waking hours and puts you to sleep when you need to reset. This mechanism represents an internal nodding off point that is separate from external factors. When it is turned off or out of use, sleep deficits build up.

'What makes us go to sleep at night is probably a combination of the two mechanisms,' says Professor Miesenböck. 'The body clock says it's the right time, and the sleep switch has built up pressure during a long waking day.'

The work in fruit flies allowed the critical part of the sleep switch to be discovered. 'We discovered mutant flies that couldn't catch up on their lost sleep after they had been kept awake all night,' says Dr Jeffrey Donlea.

Flies stop moving when they go to sleep and require more disturbance to get them up. Sleep-deprived flies are prone to nodding off and are cognitively impaired -- they have severe learning and memory deficits, much as sleep loss in humans leads to problems.

Professor Miesenböck says: 'The sleep homeostat is similar to the thermostat in your home. A thermostat measures temperature and switches on the heating if it's too cold. The sleep homeostat measures how long a fly has been awake and switches on a small group of specialized cells in the brain if necessary. It's the electrical output of these nerve cells that puts the fly to sleep.'

In the mutant flies, the researchers were able to show a key molecular component of the electrical activity switch is broken and the sleep-inducing neurons are always off, causing insomnia.

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Autism may be due to specific chemical switch

A study shows that autism may be caused by a specific faulty chemical switch that does not get turned on causing the brain to not develop normally.

Autism may result from a faulty chemical switch that doesn't get flipped in time to help the brain develop normally, a new research study suggests.

Building on what they hope will be an important insight into the cause of autism, French researchers are testing a high blood pressure medication on dozens of European children with autism.

The team, which has a financial stake in the drug, has tried it on 30 children with autism; now they are testing it in more, hoping to improve core characteristics of autism for the first time.

There are drugs to treat some of autism's symptoms, but none that address the underlying social and communication difficulties and repetitive behaviors, which define the condition. Previous attempts to develop an effective drug against the condition, which affects at least one in 88 U.S. schoolchildren, have either failed or are also still experimental.

In a study out today in the journal Science, the researchers offer an explanation for the promise of their drug, bumetanide, a generic diuretic long used to treat the fluid retention of high blood pressure.

The researchers found that the drug, given during pregnancy, could reverse autism symptoms in newborn mice bred with a genetic condition that often causes autism in people, and in rats exposed to the epilepsy drug valproic acid, which is known to trigger autism.

They suspect that bumetanide is flipping a chemical switch in the brain — changing the chemical GABA from stimulating electrical activity in the brain to tamping it down. This switch needs to be flipped during or near birth for the brain to develop normally, says lead researcher Yehezkel Ben-Ari of the French Institut National de la Santé et de la Recherche Médicale, in Marseilles, France.

Because this switch fails to flip in rodents with two very different triggers of autism, the researchers say they may have found an underlying cause of the condition.

That is a "pretty incredible finding and really great," says Andrew Zimmerman, a pediatric neurologist and autism expert at the University of Massachusetts Medical School in Worcester, Mass.

He and other researchers note that it's too early for people to try the drug outside of carefully watched clinical trials. There are just so many unknowns, from what the drug will do to the developing brain to how much of the drug to give and when.

"So many things cure cancer in mice and rats, and so many things cure all kinds of things and then when we give them to humans they have adverse affects and don't fix the problems we thought they could fix," says Gary Goldstein, president and CEO of the Kennedy Krieger Institute, a Baltimore-based clinic and research center. "I wouldn't give it to my child, I can tell you that."

Ben-Ari and his colleagues have patented a version of bumetanide and formed a company, Neurochlore, in Marseilles, to test the drug in children. He says bumetanide should not be given to pregnant women — despite his success with rodents — because it is impossible to determine which children will go on to develop autism and unethical to test on healthy ones.

It should be used as early in childhood as possible, Ben-Ari says, and his team is testing the drug in children as young as 2. Autism is typically diagnosed around age 4, but experts are working to push that diagnosis earlier. It is widely believed that the sooner treatment begins, the more effective it is likely to be.

Ben-Ari says he is hopeful that the drug will show benefits across a broad spectrum of children with autism, but behavioral therapy and possibly other pharmaceutical treatments will likely still be needed, too, he says.

"It's important for people to understand there is no drug to cure a medical disease as complicated as autism," he says.

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