MSGID: 1:317/3 63fd8369   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Early-life stress can disrupt maturation of brain's reward circuits,   
   promoting disorders    
    New therapeutic target for treating mental illness    
      
     Date:   
         February 27, 2023   
     Source:   
         University of California - Irvine   
     Summary:   
         A new brain connection can explain how early-life stress and   
         adversity trigger disrupted operation of the brain's reward   
         circuit, offering a new therapeutic target for treating mental   
         illness. Impaired function of this circuit is thought to underlie   
         several major disorders, such as depression, substance abuse and   
         excessive risk-taking.   
      
      
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   FULL STORY   
   ==========================================================================   
   A new brain connection discovered by University of California, Irvine   
   researchers can explain how early-life stress and adversity trigger   
   disrupted operation of the brain's reward circuit, offering a new   
   therapeutic target for treating mental illness. Impaired function of   
   this circuit is thought to underlie several major disorders, such as   
   depression, substance abuse and excessive risk-taking.   
      
      
   ==========================================================================   
   In an article recently published online in Nature Communications,   
   Dr. Tallie Z.   
      
   Baram, senior author and UCI Donald Bren Professor and Distinguished   
   Professor in the Departments of Anatomy & Neurobiology, Pediatrics,   
   Neurology and Physiology & Biophysics, and Matt Birnie, lead author and   
   a postdoctoral researcher, describe the cellular changes in the brain's   
   circuitry caused by exposure to adversity during childhood.   
      
   "We know that early-life stress impacts the brain, but until now,   
   we didn't know how," Baram said. "Our team focused on identifying   
   potentially stress- sensitive brain pathways. We discovered a new   
   pathway within the reward circuit that expresses a molecule called   
   corticotropin-releasing hormone that controls our responses to   
   stress. We found that adverse experiences cause this brain pathway to   
   be overactive."  "These changes to the pathway disrupt reward behaviors,   
   reducing pleasure and motivation for fun, food and sex cues in mice,"   
   she said. "In humans, such behavioral changes, called 'anhedonia,' are   
   associated with emotional disorders. Importantly, we discovered that when   
   we silence this pathway using modern technology, we restore the brain's   
   normal reward behaviors."  Researchers mapped all the CRH-expressing   
   connections to the nucleus accumbens, a pleasure and motivation hub in   
   the brain, and found a previously unknown projection arising from the   
   basolateral amygdala. In addition to CRH, projection fibers co-expressed   
   gama-aminobutyric acid. They found that this new pathway, when stimulated,   
   suppresses several types of reward behaviors in male mice.   
      
   The study involved two groups of male and female mice. One was exposed to   
   adversity early in life by living for a week in cages with limited bedding   
   and nesting material, and the other was reared in typical cages. As   
   adults, the early adversity-experiencing male mice had little interest in   
   sweet foods or sex cues compared to typically reared mice. In contrast,   
   adversity-experiencing females craved rich, sweet food. Inhibiting the   
   pathway restored normal reward behaviors in males, yet it had no effect   
   in females.   
      
   "We believe that our findings provide breakthrough insights into the   
   impact of early-life adversity on brain development and specifically on   
   control of reward behaviors that underlie many emotional disorders. Our   
   discovery of the previously unknown circuit function of the basolateral   
   amygdala-nucleus accumbens brain pathway deepens our understanding of   
   this complex mechanism and identifies a significant new therapeutic   
   target." Baram said. "Future studies are needed to increase our   
   understanding of the different and sex-specific effects of early-life   
   adversity on behavior."  Team members include Annabel K. Short,   
   postdoctoral researcher, Lara Taniguchi, graduate student, Aidan Pham,   
   lab assistant, and co-corresponding author Yuncai Chen, project scientist,   
   from Department of Pediatrics; Gregory B. de Carvalho, graduate student,   
   Benjamin G. Gunn, assistant project scientist; Christy A.   
      
   Itoga, researcher; Xiangmin Xu, professor; Lulu Y. Chen, assistant   
   professor; from the Department of Anatomy & Neurobiology; and Stephen   
   V. Mahler, associate professor from the Department of Neurobiology   
   and Behavior.   
      
   This work was supported by National Institute of Health grants   
   P50 MH096889, MH73136, U01DA053826 NS108296 P50 DA044118, P50   
   MH096889 Seed Award FG23670, The Bren Foundation, a George E. Hewitt   
   Foundation for Biomedical Research Fellowship and a British Society for   
   Neuroendocrinology Project Support Grant BSN-5646342.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Mental_Health_Research # Brain_Tumor #   
                   Psychology_Research # Birth_Defects   
             o Mind_&_Brain   
                   # Brain-Computer_Interfaces # Disorders_and_Syndromes #   
                   Mental_Health # Intelligence   
       * RELATED_TERMS   
             o Psychopathology o Psychoactive_drug o Mental_illness o   
             Psychosurgery o Integrated_circuit o Brain_damage o Psychiatry   
             o Sleep_disorder   
      
   ==========================================================================   
   Story Source: Materials provided by   
   University_of_California_-_Irvine. Note: Content may be edited for style   
   and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Matthew T. Birnie, Annabel K. Short, Gregory B. de Carvalho, Lara   
         Taniguchi, Benjamin G. Gunn, Aidan L. Pham, Christy A. Itoga,   
         Xiangmin Xu, Lulu Y. Chen, Stephen V. Mahler, Yuncai Chen, Tallie   
         Z. Baram.   
      
         Stress-induced plasticity of a CRH/GABA projection disrupts   
         reward behaviors in mice. Nature Communications, 2023; 14 (1) DOI:   
         10.1038/ s41467-023-36780-x   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/02/230227161434.htm   
      
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