`Fight or flight' - unless internal clocks are disrupted, study in mice
shows

Date:
October 1, 2021
Source:
Washington University in St. Louis
Summary:
Daily release of hormones depends on the coordinated activity
of clocks in two parts of the brain, a finding that could have
implications for human diseases.



FULL STORY ==========================================================================
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, 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, 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.

The same hormones that help humans prepare for dealing with the morning
commute or a challenging work day also help mice meet their nightly step
goals on the running wheel.

Using a novel neuronal recording approach, Jones and Herzog recorded
brain activity in individual mice for up to two weeks at a time.



========================================================================== "Recording activity from identified types of neurons for such a long
period of time is difficult and data intensive," Herzog said. "Jeff
pioneered these methods for long-term, real-time observations in behaving animals." Using information about each mouse's daily rest-activity
and corticosterone secretion, along with gene expression and electrical activity of targeted neurons in their brains, the scientists discovered
a critical circuit between the SCN and neurons in the PVN that produce
the hormone that triggers release of glucocorticoids.

Turns out, it's not enough for the neurons in the SCN to send out daily signals; the 'local' clock in the PVN neurons also has to be working
properly in order to produce coordinated daily rhythms in hormone release.

Experiments that eliminated a clock gene in the circadian-signal-receiving
area of the brain broke the regular daily cycle.

"There's certain groups of neurons in the SCN that communicate timing information to groups of neurons in the PVN that regulate daily hormone release," Jones said. "And for a normal hormone rhythm to proceed, you
need clocks in both the central pacemaker and this downstream region
to work in tandem." The findings in mice could have implications for
humans down the road, Jones said. Future therapies for cortisol-related diseases and genetic conditions in humans will need to take into account
the importance of a second internal clock.

========================================================================== Story Source: Materials provided by
Washington_University_in_St._Louis. Original written by Talia
Ogliore. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jeff R. Jones, Sneha Chaturvedi, Daniel Granados-Fuentes, Erik
D. Herzog.

Circadian neurons in the paraventricular nucleus entrain and sustain
daily rhythms in glucocorticoids. Nature Communications, 2021; 12
(1) DOI: 10.1038/s41467-021-25959-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211001082614.htm

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