MSGID: 1:317/3 6274a4f1   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    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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