Tiny Worm Reveals Why Melatonin Makes Us Sleepy

Melatonin (Mel) is a hormone the body produces to inform the brain when it's time to sleep typically during nighttime. Although it is also a dietary supplement recommended for those who have prolonged jet lag or other sleeping problems, scientists know very little about how the brain responds to melatonin to promote sleep.

In a recent study by a team from the University of Connecticut, they discovered how melatonin promotes sleep in the worm Caenorhabditis elegans. The results have implications of how the hormone works in the human brain as well.

When it's dark, the body produces more melatonin, regulating the body clock by informing the brain that it is time to sleep. Those who produce low levels of melatonin during the night typically have sleeping problems such as Delayed Sleep-Wake Phase Disorder or most likely work during the night.

Brain Structure of Worms

In 2018, Dr. Zhao-Wen Wang and his team made a detailed wiring diagram of the C. elegans locomotion neural circuit. He also received a grant from the NIH National Institute of Neurological Disorders and Stroke to study the tiny worm's chemical synapses (one-way transmitters) and gap junctions (two-way transmitters).

The C. elelgans is only one millimeter long but has revealed how different neurons affect body movement. In the new study, the researchers identified how melatonin activates the potassium channel or BK channel through receptors called PCDR-1 and SLO-1.

Before the hormone triggers the BK channel, previous research determined that mammals have two Mel receptors called MT1 and MT2. However, Mel's "sleep-promoting effect remains mysterious."

The BK channel controls levels of neurotransmitters released between neurons. In the C. elegans brain, the team observed that the two Mel receptors needed for the regulation of neurotransmitter release. As a result, worms that lack the receptor or melatonin secretion had less sleep.

Understanding Melatonin

Sleeping behaviors of worms are similar to mammals, explained Bojun Chen. "we tested whether light and darkness conditions may have different effects on Mel's action because the BK channel level in mammals varies with the day/night cycles," wrote the authors.

They also discovered that although a majority of neurons are less active when the worms were asleep, sleep-promoting neurons remained active. There was also evidence that the potassium channel plays a role in the brain switching from sleep to wake states depending on the levels of octopamine (a molecule that promotes wakefulness) and Mel. To further determine if people have the same response to melatonin within the BK channel in the brain, the researchers will experiment with mice models.

Moreover, the BK channel is not only associated with sleep, but also play a role with changes in behavior or mood, blood pressure levels, and epilepsy. Understanding more about how Mel works in the brain could lead to improved treatment of diseases associated with the potassium channel.

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