Let’s talk nemuri: the gene that induces the need to sleep

Let’s talk nemuri: the gene that induces the need to sleep
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Humans spend almost one-third of their lives sleeping, yet sleep is still one of biology’s most enduring mysteries – could nemuri unlock this?

Published in Science, researchers from the Perelman School of Medicine at the University of Pennsylvania, USA, studied over 12,000 lines of fruit flies, and found a single gene, called nemuri, that increases the need for sleep.

What do you know about the nemuri gene?

Previously, little was known about what genetic or molecular forces drive the need to sleep, until now.

The NEMURI protein combats germs with its inherent antimicrobial activity and is secreted by cells in the brain to drive prolonged, deep sleep after an infection.

Amita Sehgal, PhD, a professor of Neuroscience and director of Penn’s Chronobiology Program, explains: “While it’s a common notion that sleep and healing are tightly related, our study directly links sleep to the immune system and provides a potential explanation for how sleep increases during sickness.”

Nemuri appears to kill microbes

Without the nemuri gene, flies were more easily awakened during daily sleep, and their acute need for an increase in sleep, induced by sleep deprivation or infection, decreased.

On the other hand, sleep deprivation, which increases the need for sleep, and to some extent infection, stimulated nemuri to be expressed in a small set of fly neurons nestled close to a known sleep-promoting structure in the brain.

Overexpression of nemuri increased sleep in bacteria-infected flies and led to their increased survival compared to non-infected control flies.

In response to infection, nemuri appears to kill microbes, most likely in the peripheral parts of the fruit fly body and increases sleep through its action in the brain.

Multiple molecules like nemuri , which is an antimicrobial peptide (AMP), have various functions that help fight infection, but its sleep-promoting role may be just as important for host defence, the researchers suggest, given that increased sleep during sickness promotes survival in the flies.

Other implications in human sleep

What’s more, the authors note that cytokines such as interleukin-1 (IL-1), an immune cell molecule, are implicated in human sleep. IL-1 can function in the same pathway as AMPs, and it accumulates after prolonged wakefulness and appears to promote sleep.

In mammals, cytokines can encourage production of AMPs, but AMPS may also affect the expression of cytokines. Given this interwoven relationship, the researchers conclude that NEMURI is a working link between immune function and sleep.

Hirofumi Toda, PhD, a postdoctoral fellow in Sehgal’s lab and first author adds: “The nemuri protein is a genuine driver of keeping sleep on track under conditions of high sleep need like when we’re sick.”

“In the next phase of our work, we plan to investigate the mechanism by which nemuri drives sleep.”

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