Global Neuropeptidome Profiling in Response to Predator Stress in Rat: Implications for Post-Traumatic Stress Disorder

Traumatic stress triggers or exacerbates multiple psychiatricillnesses,including post-traumatic stress disorder (PTSD). Nevertheless, theneurophysiological mechanisms underlying stress-induced pathologyremain unclear, in part due to the limited understanding of neuronalsignaling molecules, such as neuropeptides, in this process. Here,we developed mass spectrometry (MS)-based qualitative and quantitativeanalytical strategies to profile neuropeptides in rats exposed topredator odor (an ethologically relevant analogue of trauma-like stress)versus control subjects (no odor) to determine peptidomic alterationsinduced by trauma. In total, 628 unique neuropeptides were identifiedacross 5 fear-circuitry-related brain regions. Brain-region-specificchanges of several neuropeptide families, including granin, ProSAAS,opioids, cholecystokinin, and tachykinin, were also observed in thestressed group. Neuropeptides from the same protein precursor werefound to vary across different brain regions, indicating the site-specificeffects of predator stress. This study reveals for the first timethe interaction between neuropeptides and traumatic stress, providinginsights into the molecular mechanisms of stress-induced psychopathologyand suggesting putative novel therapeutic strategies for disorderssuch as PTSD.