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Lack of Sleep Leads to Shut down Production of Essential Brain Proteins

Natural circadian rhythm is disrupted by not enough sleep

As researchers continue to discover the necessary benefits of a good sleep, two new studies, both published in the Science, have deepened our understanding as to why sleep is essential for cognitive and physical health.

According to a report in Scientific American, the studies showed that the downside of sleep deprivation leads to a deficit arises in molecules needed for neurons to communicate efficiently.

As per the findings published in both the papers, place synapses at center stage. These nodes of neuronal communication, researchers show, are where internal preparations for sleep and the effects of our sleep-related behaviors converge.

Cellular timekeepers rhythmically prep areas around the synapses in anticipation of building synaptic proteins during slumber. But the new findings indicate neurons don’t end up building these critical proteins in the absence of sleep.

While applauding the two new researches and calling them fascinating, Robert Greene, a neuroscientist at the University of Texas Southwestern Medical Center, who was not involved in the study, said, “The results suggest the brain is getting prepared for an event, but it doesn’t mean you actually follow through on doing it,”.

Greene said, “These studies confirm a long-suspected connection, between internal timekeeping and sleep behaviors”.

When we become sleepy, two factors are in play: “sleep pressure,” or the growing allure of a beckoning pillow as waking time lengthens, and our internal clock sounding the signal that the usual point for shut-eye has arrived.

In one of the two studies, Sara B. Noya of the Institute of Pharmacology and Toxicology at the University of Zurich and her colleagues showed that in mice, the internal clock regulates the rhythmic generation of instructions, or transcripts, for making proteins. Giving in to sleep pressure and hitting the hay, they found, triggers the final steps of protein production.

Noya’s team discovered that at two peak times in the 24-hour day, just before waking and sleeping, neurons in cognition-related brain areas packed a timekeeping cell’s signaling stations with these transcripts.

The “sleep time” transcripts tended to be for proteins that regulate building other proteins, while the “wake time” instructions were for proteins linked to synapse function. These stashed molecules set the stage for the rapid refreshing of synapses during sleep. Mice lacking important clock genes did not show these peaks.

With a regular sleep-wake cycle, the proteins built using these instructions also showed peak production at dawn and dusk.

In sleep-deprived mice, however, Noya and her colleagues demonstrated that the cell still produced many of the transcripts but did not build the related proteins. That result implies sleeping regulates the final, protein-building step in ensuring robust synapses.

Not all proteins that the cell makes necessarily go into active service, though. In a companion paper, Franziska Brüning of the Ludwig Maximilian University of Munich and the Max Planck Institute of Biochemistry in Martinsried, Germany, and her colleagues explored the rhythmic use of those that do. Attachment or removal of a phosphate molecule acts as a toggle to turn proteins on or off, so the investigators took a close look at this process. They found levels of proteins that had been tagged with phosphates also peaked twice, with the bigger peak occurring just before waking. And as with proteins in the other study, sleep deprivation flattened these peaks.

The researchers made their measurements every four hours, an advance on earlier studies that usually looked at a single time point during a 24-hour period, says Chiara Cirelli, a neuroscientist at the University of Wisconsin–Madison, who co-wrote a commentary accompanying the two papers. “It’s a very comprehensive analysis across the entire light-dark cycle,” she says.

Cirelli emphasizes the importance of isolating the synaptic regions where these molecules accumulate and are produced. The researchers pinned down when transcripts were positioned at the ready and when proteins tagged with phosphates or not were made or used, she says.

Maria Robles, a neuroscientist at Ludwig Maximilian University of Munich and a co-author of both papers, says the findings distinguishing the different stages of protein production and activity are eye-opening, revealing the brain has “a beautiful way to control” these molecules.

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