It is already known that getting a good night’s sleep becomes more difficult as we age, but the biological reason behind this is still poorly understood.
A team of US scientists has identified how the brain circuitry involved in the regulation of sleep and wakefulness degrades over time in mice, which they say paves the way for better drugs for humans.
“More than half of people aged 65 and over complain about the quality of their sleep,” Luis de Lecea, a professor at Stanford University and co-author of a study on the finding published in the journal Science on Thursday, told AFP. ).
Research has shown that lack of sleep is linked to an increased risk of a range of health problems: from high blood pressure to heart attacks to diabetes, depression and the buildup of brain plaques linked to Alzheimer’s disease.
Insomnia is often treated with a class of drugs known as hypnotics, such as zolpidem, but they don’t work very well in the elderly population.
For the new study, De Lecea and his colleagues decided to investigate hypocretins, important brain chemicals that are generated only by a small group of neurons in the hypothalamus. This region of the brain is located between the eyes and the ears.
Of the billions of neurons in the brain, only about 50,000 produce hypocretins. In 1998, De Lecea and other scientists discovered that hypocretins transmit signals that play a vital role in stabilizing wakefulness.
As many species experience fragmented sleep as they age, it is hypothesized that this is caused by the same mechanism in all mammals. Previous research has shown that the degradation of hypocretins causes narcolepsy in humans, dogs and mice.
The team selected young mice, aged between three and five months, and old mice, aged between 18 and 22 months, and used fiber-borne light to stimulate specific neurons. They recorded the results, using imaging techniques.
They found that the older mice lost approximately 38% of the hypocretins, compared with the younger ones. It was further observed that the remaining hypocretins in the older mice were more stimulable and more easily detonated, making the animals more likely to wake up.
This may be due to the deterioration, over time, of “potassium channels”, which are important biological switches for the functions of many types of cells.
“Neurons tend to be more active and fire more, and if they fire more, you wake up more often,” explained De Lecea.
Identifying the specific pathway responsible for sleep loss could lead to better medication, argue Laura Jacobson and Daniel Hoyer of Australia’s Florey Institute for Neuroscience and Mental Health in a related opinion article.
Current treatments, such as hypnotics, “can induce cognitive illness and falls,” and drugs that target a specific channel may work better, they added.
These drugs will need to be tested in clinical trials, but an existing drug known as retigabine, currently used to treat epilepsy and targeting a similar pathway, could hold promise, according to De Lecea.
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