Why hungry worms take risks
Scientists defined the molecular movement that connects gut to brain to behavior
Date:
May 5, 2022
Source:
Salk Institute
Summary:
Whether it's making rash decisions or feeling grumpy, hunger can
make us think and act differently -- 'hangry,' even. But little
is known about how hunger signals in the gut communicate with
the brain to change behavior. Now, scientists are using worms as
a model to examine the molecular underpinnings and help explain
how hunger makes an organism sacrifice comfort and make risky
decisions to get a meal.
FULL STORY ========================================================================== Whether it's making rash decisions or feeling grumpy, hunger can make
us think and act differently -- "hangry," even. But little is known
about how hunger signals in the gut communicate with the brain to change behavior. Now, Salk scientists are using worms as a model to examine the molecular underpinnings and help explain how hunger makes an organism
sacrifice comfort and make risky decisions to get a meal.
========================================================================== Their latest findings, published in PLOS Genetics on May 5, 2022, reveal
that proteins in intestinal cells move dynamically to transmit signals
about hunger, ultimately driving worms to cross toxic barriers to reach
food. Similar mechanisms may also occur in humans.
"Animals, whether it's a humble worm or a complex human, all make choices
to feed themselves to survive. The sub-cellular movement of molecules
could be driving these decisions and is maybe fundamental to all animal species," says senior author Sreekanth Chalasani, associate professor
in Salk's Molecular Neurobiology Laboratory.
Chalasani and team used a tiny worm called Caenorhabditis elegans as a
model to determine how hunger leads to behavioral changes. The researchers created a barrier of copper sulfate, which is a known worm repellant,
between the hungry wormsand a food source. They observed that if the
worms were deprived of food for two-to-three hours, then they were more
willing to traverse the toxic barrier compared to well-fed worms.
Using genetic tools and imaging techniques, the researchers then
investigated the gut molecules that might be sending signals to the
brain. They found that specific transcription factors, proteins that turn
genes "on" and "off," shifted locations in hungry animals. Normally, transcription factors hang out in the cell's cytoplasm and move into
the nucleus only when activated - - similar to the way we live at home
but go into the office to get work done.
The team was surprised to discover that these transcription factors,
called MML-1 and HLH-30, move back to the cytoplasm when the worm
is hungry. When the scientists deleted these transcription factors,
hungry worms stopped trying to cross the toxic barrier. This indicates
a central role for MML-1 and HLH-30 in controlling how hunger changes
animal behavior.
In a follow-up experiment, the researchers also discovered that a
protein called insulin-like peptide INS-31 is secreted from the gut
when MML-1 and HLH- 30 are on the move. Neurons in the brain, in turn,
make a receptor that might detect the INS-31secretions.
To sum it up: A lack of food leads to movement of MML-1 and HLH-30,
which could promote the secretion of INS-31. INS-31 peptides then
bind receptors on neurons to relay hunger information and drive risky food-seeking behavior.
"C. elegansare more sophisticated than we give them credit for," says
co-first author Molly Matty, a postdoctoral fellow in Chalasani's
lab. "Their intestines sense a lack of food and report this to the
brain. We believe these transcription factor movements are what guide the animal into making a risk- reward decision, like traversing an unpleasant barrier to get to food." Next, the scientists will further investigate
the dynamic nature of these transcription factors and underlying
mechanisms. With further work, these findings could provide insight into
how other animals, such as humans, prioritize basic needs over comfort.
This work was supported by the Rita Allen Foundation, W.M. Keck
Foundation, National Institutes of Health (grant R01MH096881), National
Science Foundation (postdoctoral research fellowship 2011023 and two
graduate research fellowships), Glenn Foundation and Socrates Program
(grant NSF-742551).
========================================================================== Story Source: Materials provided by Salk_Institute. Note: Content may
be edited for style and length.
========================================================================== Journal Reference:
1. Molly A. Matty, Hiu E. Lau, Jessica A. Haley, Anupama Singh, Ahana
Chakraborty, Karina Kono, Kirthi C. Reddy, Malene Hansen,
Sreekanth H.
Chalasani. Intestine-to-neuronal signaling alters risk-taking
behaviors in food-deprived Caenorhabditis elegans. PLOS Genetics,
2022; 18 (5): e1010178 DOI: 10.1371/journal.pgen.1010178 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/05/220505143729.htm
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