How Intermittent Hypoxia Disrupts Circadian Rhythms

Published October 2021 | Genes

More than 1 billion people worldwide experience episodes of oxygen desaturation (intermittent hypoxia) as a result of obstructive sleep spnea (OSA). Untreated OSA can cause a wide range of health conditions including heart disease, neurological, and metabolic disorders.

Scientists have suspected that IH interferes with circadian rhythms. But the body has many clocks operating in many tissues. Which ones are affected the most when IH occurs?

Circadian medicine researchers at Cincinnati Children’s, led by Bala S.C. Koritala, PhD, and David Smith, MD, PhD, have shed light on this mystery by studying how exposure to IH affects the circadian rhythms of core clock genes in mice. These genes are known to play roles in regulating several physiological functions including daily activity, blood pressure, and core body temperature.

The team found that the brain’s circadian clock was highly affected by IH as compared to the liver’s clock. In particular, the Arntl and Nr1d1 genes in the brain and Cry2 in the liver lost their circadian gene expression as a consequence of IH exposure.

Future studies will seek to determine how disrupted clocks affect the OSA disease process.

“In summary, our results reinforce the concept that the clock response to IH is tissue-dependent,” Smith says. “Our observations also provided insights to potential underlying etiologies of circadian rhythm-associated health conditions.”

In addition to Koritala and Smith, seven people at Cincinnati Children’s were contributing co-authors: Yin Yeng Lee, PhD, Shweta Bhadri, MS, Laetitia Gaspar, PhD, Corinne Stanforth, BS, Gang Wu, PhD, Marc Ruben, PhD, and Lauren Francey, MS.