Global Neuropeptidome Profiling in Response to Post-traumatic Stress Disorder in Rat

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that affects the health of a wide range of the population. However, its underlying neurophysiological mechanisms remain unclear due to the limited understanding of neuronal signaling molecules such as neuropeptides. Here, we developed mass spectrometry (MS) based qualitative and quantitative analysis to profile the neuropeptides in the control and predator odor exposure rat PTSD model group. In total, 628 unique neuropeptides can be identified across 5 fear circuitry-related brain regions. Meanwhile, brain region-specific changes of serval neuropeptide families including granin, ProSAAS, opioid peptide, cholecystokinin, and tachykinin can be observed in the PTSD group. Neuropeptides from the same protein precursor were also found to vary in different brain regions. This study reveals for the first time the interaction between neuropeptides and severe stress, providing insights into the molecular mechanism of PTSD and corresponding therapeutic strategy.