AUG 23, 2021 9:48 AM PDT

A Conductor of the Circadian Rhythm is Identified

WRITTEN BY: Carmen Leitch

The daily cycle of the planet is reflected in the biology of plants and animals. Even our cells are influenced by what's known as the circadian rhythm, which has been connected to many physiological processes including metabolism, cardiac function, and mental health, among others. Dysfunction in the circadian rhythm has also been linked to disease.

Microscopic image of the mouse suprachiasmatic nucleus, the brain region responsible for controlling circadian rhythms. / Credit: UT Southwestern Medical Center

Researchers have now determined that a gene called Npas4 may act as a master regulator of the body's clock, and helps reset the body clock to daylight. In a new study reported in Neuron, scientists used an animal model to assess gene expression at the single-cell level in a region of the brain that's known to play a crucial role in setting the circadian rhythm, the suprachiasmatic nucleus (SCN). Gene activity was examined after the animals had been exposed to light.

“To reset the circadian clock, you ultimately need to reset its molecular gears,” said study leader and Howard Hughes Medical Institute Investigator Joseph S. Takahashi, Ph.D., Chair of Neuroscience at UTSW. Light helps set the circadian clock, noted Takahashi. Cells in the SCN react to light sensed by the retina in the eye.

In the SCN, there seems to be three different types of neurons in the SCN that can respond to light-induced signaling. In all of these cells, the activity changed in genes that are influenced by the protein encoded by Npas4 (neuronal PAS domain protein 4).

When a mouse model was engineered in which Npas4 would not respond to light, the activity of hundreds of circadian clock genes was disrupted. These animals also gained about an hour in their body clock so their daily cycle lengthened to 25 instead of 24 hours. This evidence indicates that Npas4 masters the regulation of some genes that are activated by light, suggested Takahashi.

This work has given us some new insight into the molecular mechanisms of the circadian clock, and may one day help researchers develop therapeutics that can mitigate the negative effects of circadian rhythm disruptions, like what's caused by shift work, insomnia, or jet lag.

Sources: UT Southwestern (UTSW), Neuron

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