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February 25, 2022 11:51 AM
In 1998, de Lecea and other scientists discovered that hypocretins transmit signals that play a vital role in stabilising wakefulness.
Since many species experience fragmented sleep as they grow old, it’s hypothesised that the same mechanisms are at play across mammals, and prior research had shown degradation of hypocretins leads to narcolepsy in humans, dogs and mice.
The team selected mice young (three to five months) and old (18 to 22 months), and used light carried by fibres to stimulate specific neurons. They recorded the results using imaging techniques.
What they found was that the older mice had lost approximately 38% of hypocretins compared with the younger mice.
They also discovered that the hypocretins remaining in the older mice were more excitable and easily triggered, making the animals more prone to waking up.
This might be because of the deterioration over time of “potassium channels”, which are biological on-off switches critical to the functions of many types of cells.
“The neurons tend to be more active and fire more, and if they fire more, you wake up more frequently,” said de Lecea.
Identifying the specific pathway responsible for sleep loss could lead to better drugs, argued Laura Jacobson and Daniel Hoyer, of Australia’s Florey Institute of Neuroscience and Mental Health, in a related commentary article.
Current treatments such as hypnotics “can induce cognitive complaints and falls”, and medicines that target the specific channel might work better, they said.
These will need to be tested in clinical trials, but an existing drug known as retigabine – currently used to treat epilepsy and which targets a similar pathway – could be promising, said de Lecea.
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