With or without sleep: activity of sleep neurons


image: Activation of the sleep neuron elicits a stress gene expression response throughout the worm’s body, visualized here in red by staining for HSP-12.6, a heat shock protein necessary for survival.
to see After

Credit: © Anastasios Koutsoumparis

Sleep is an essential process that influences all the tissues and systems of our body. At the molecular level, sleep induces the expression of genes that help maintain the brain and body. Missing a night’s sleep is a huge challenge for the body. It activates genes that react to stress and protect the body from the consequences of sleep deprivation. Part of this stress response is the activation of protective genes in the so-called FOXO pathway. This pathway is involved in a multitude of cellular processes that globally contribute to recovery, survival and longevity. How sleep and lack of sleep trigger these changes in gene expression has not been understood. To answer this long-standing question, scientists at the Center for Biotechnology (BIOTEC) at the Technical University of Dresden, led by Professor Henrik Bringmann, studied sleep in C.elegans toward.

“To trigger sleep, our body must turn off the waking state. There is a special set of sleep neurons for this task. These sleep neurons send signals that shut down other neurons responsible for wakefulness and thus promote sleep. Humans have thousands of these sleep neurons located in various centers of the brain,” says Professor Henrik Bringmann. “Which makes C.elegans a wonderful minimal model to study sleep is that it has only one active key neuron in sleep that induces sleep.

It’s all about the sleep neuron

Bringmann’s team wanted to test how this sleep neuron affects changes in gene expression during sleep. “Sleep neurons are active during sleep, and they are even more activated during sleep deprivation. It may seem counter-intuitive at first, but that’s because our body acts like a homeostat. If something throws it off balance, our body tries to compensate to bring it back into balance. In this case, the disturbed sleep causes the body to activate sleep neurons more and more, in an attempt to force sleep,” explains Professor Bringmann.

The team genetically modified two versions of the C.elegans toward. One type had his sleep neuron permanently inactive and the other permanently active. “These two extreme situations resulted in the loss of sleep. This was an experimental advantage for us, as we were able to test whether the sleep neuron controls gene expression independently of sleep,” says Professor Bringmann.

As a result, the scientists observed that the expression of stress response and protective genes decreased when the sleep neuron was turned off. In contrast, the expression of these genes increased when the sleep neuron was continuously active. “These results show that the expression of the protective gene is a function of the activity of sleep neurons”, explains Professor Bringmann.

The results provide a new interpretation of the consequences of sleep disturbances in C.elegans. “Our experiments suggest that the protective gene expression response observed when sleep is disturbed is rather not caused by the actual loss of sleep, but by the overactivation of the sleep neuron,” explains Professor Bringmann.

Lessons from the worm

The results provide an unexpected link between sleep neuron activity and gene expression. While the results come from the C.elegans worm, they present a potential paradigm shift for understanding the consequences of sleep deprivation and insomnia in other animals as well.

“Sleep disturbances are known to cause neurons that are active during sleep to become over-activated in many animals,” adds Professor Bringmann. “It could be that the activity of sleep neurons controls the stress response and the expression of protective genes linked to longevity in other animals and perhaps even in humans. These questions constitute an interesting topic for further study.

Original publication
Anastasios Koutsoumparis, Luisa M.Welp, Alexander Wulf, Henning Urlaub, David Meierhofer, Stefan Börno, Bernd Timmermann, InkaBusac, Henrik Bringmann: Depolarization of sleep neurons promotes changes in expression of protective genes and activation of FOXO. Current biology (May 2022)
Link: https://doi.org/10.1016/j.cub.2022.04.012

About the Biotechnology Center (BIOTEC)
The Biotechnology Center (BIOTEC) was founded in 2000 as a central scientific unit of the TU Dresden with the aim of combining modern approaches in molecular and cell biology with the traditionally strong engineering in Dresden. Since 2016, BIOTEC has been part of the central science unit “Center for Molecular and Cellular Bioengineering” (CMCB) at TU Dresden. BIOTEC promotes developments in research and teaching in the field of molecular bioengineering research and combines approaches in cell biology, biophysics and bioinformatics. It plays a central role in the research priority area of ​​Health Sciences, Biomedicine and Bioengineering at TU Dresden.

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