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

Traumatic stress triggers or exacerbates multiple psychiatric
illnesses,
including post-traumatic stress disorder (PTSD). Nevertheless, the
neurophysiological mechanisms underlying stress-induced pathology
remain unclear, in part due to the limited understanding of neuronal
signaling molecules, such as neuropeptides, in this process. Here,
we developed mass spectrometry (MS)-based qualitative and quantitative
analytical strategies to profile neuropeptides in rats exposed to
predator odor (an ethologically relevant analogue of trauma-like stress)
versus control subjects (no odor) to determine peptidomic alterations
induced by trauma. In total, 628 unique neuropeptides were identified
across 5 fear-circuitry-related brain regions. Brain-region-specific
changes of several neuropeptide families, including granin, ProSAAS,
opioids, cholecystokinin, and tachykinin, were also observed in the
stressed group. Neuropeptides from the same protein precursor were
found to vary across different brain regions, indicating the site-specific
effects of predator stress. This study reveals for the first time
the interaction between neuropeptides and traumatic stress, providing
insights into the molecular mechanisms of stress-induced psychopathology
and suggesting putative novel therapeutic strategies for disorders
such as PTSD.