Arts & Sciences

‘Fight or flight’ – unless internal clocks are disrupted, study in mice shows

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For humans and animals, many aspects of normal behavior and physiology rely on the proper functioning of the body’s circadian clocks.

Here’s how it’s supposed to work: Your brain sends signals to your body to release different hormones at certain times of the day. For example, you get a boost of the hormone cortisol — nature’s built-in alarm system — right before you usually wake up.

But hormone release actually relies on the interconnected activity of clocks in more than one part of the brain. New research from Washington University in St. Louis shows how daily release of glucocorticoids depends on coordinated clock-gene and neuronal activity rhythms in neurons found in two parts of the hypothalamus, the suprachiasmatic nucleus (SCN) and paraventricular nucleus (PVN).

The new study, conducted with freely behaving mice, is published Oct. 1 in Nature Communications.

“Normal behavior and physiology depends on a near 24-hour circadian release of various hormones,” said Jeff Jones, PhD, who led the study as a postdoctoral research scholar in biology in Arts & Sciences and recently started work as an assistant professor of biology at Texas A&M University. “When hormone release is disrupted, it can lead to numerous pathologies, including affective disorders like anxiety and depression and metabolic disorders like diabetes and obesity.

“We wanted to understand how signals from the central biological clock — a tiny brain area called the SCN — are decoded by the rest of the brain to generate these diverse circadian rhythms in hormone release,” said Jones, who worked with Erik Herzog, PhD, the Viktor Hamburger Distinguished Professor in Arts & Sciences at Washington University and senior author of the new study.

The daily timing of hormone release is controlled by the SCN. Located in the hypothalamus, just above where the optic nerves cross, neurons in the SCN send daily signals that are decoded in other parts of the brain that talk to the adrenal glands and the body’s endocrine system.

“Cortisol in humans (corticosterone in mice) is more typically known as a stress hormone involved in the ‘fight or flight’ response,” Jones said. “But the stress of waking up and preparing for the day is one of the biggest regular stressors to the body. Having a huge amount of this glucocorticoid released right as you wake up seems to help you gear up for the day.”

Or for the night, if you’re a mouse.

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