Scientists have managed to restore memory formation in mice following sleep deprivation for the first time.
Researchers at the University of Pennsylvania in the US observed that sleep deprivation is tied to an impairment of protein production in the hippocampus, a brain region thought to be central to memory.
By experimentally increasing the expression of a gene involved in regulating protein synthesis in mice, they were able to prevent the deficits.
Study senior author Professor Ted Abel said: “While this study isn’t immediately translatable to humans, it does lay the groundwork for the identification of the proteins targeted by sleep deprivation.
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“This study also provides a hint about the function of sleep to drive protein synthesis and the strengthening of memories.”
Lead author Doctor Jennifer Tudor said: “We were able to essentially block the effect of sleep deprivation on memory by manipulating the expression of one gene in the hippocampus.
“It turns out that the pathway involved is also incredibly important for cell metabolism, so the connection to energy regulation is potentially very interesting.”
Prof Abel’s lab has long been interested in the effects of sleep deprivation on learning and memory. Earlier work by lab members and others has suggested sleep-dependent memory storage requires protein synthesis.
Dr Tudor said: “There was a lot of correlative data, a lot of suggestive data, but no one had actually shown in vivo that sleep deprivation impairs protein synthesis in the hippocampus.”
As a first step in the current study, published in the journal Science Signaling, the researchers confirmed this connection between sleep deprivation and protein synthesis using an antibody to a compound called puromycin that tags all newly made proteins.
After mice received an injection of the compound, they either were left to sleep or were sleep deprived for five of their normal 12 hours of sleep by gentle handling or tapping their cage.
The sleep-deprived mice had a “significantly reduced” amount of tagged proteins in their hippocampus compared to mice that got undisturbed rest.
Next, the team wanted to identify a molecular pathway responsible for the reduction in protein synthesis.
They found that not only did the mice expressing a gene called 4EBP2 have restored protein synthesis in the hippocampus, but a behavioural test showed that it also prevented memory deficits.
Dr Tudor added: “What this suggests is that there are proteins that we need in order to create a memory.
“As a next step, we’re going to identify those proteins that are actively being translated -or not - with sleep deprivation to see if we can catch them in the act and know which ones are most critically affected by sleep deprivation.”
The researchers said their findings could also lead to new research directions for other groups interested in the metabolic consequences of sleep deprivation - such as why a poor night’s sleep sometimes triggers the “munchies.”