Posttraumatic stress disorder (
PTSD) is triggered by traumatic events in 10-20% of exposed subjects. N-linked glycosylation, by modifying
protein functions, may provide an important environmental link predicting vulnerability. Our goals were (1) to find alterations in plasma N-glycome predicting stress-vulnerability; (2) to investigate how
trauma affects N-glycome in the plasma (PGP) and in three
PTSD-related brain regions (prefrontal cortex, hippocampus and amygdala; BGP), hence, uncover specific targets for
PTSD treatment. We examined male (1) controls, (2) traumatized vulnerable and (3) traumatized resilient rats both before and several weeks after electric footshock. Vulnerable and resilient groups were separated by z-score analysis of behavior. Higher freezing behavior and decreased social interest were detected in vulnerable groups compared to control and resilient rats. Innate anxiety did not predict vulnerability, but pretrauma levels of PGP10(FA1G1Ga1), PGP11(FA2G2), and PGP15(FA3G2) correlated positively with it, the last one being the most sensitive. Traumatic stress induced a shift from large, elaborate N-
glycans toward simpler neutral structures in the plasma of all traumatized animals and specifically in the prefrontal cortex of vulnerable rats. In plasma
trauma increased PGP17(A2G2S) level in vulnerable animals. In all three brain regions, BGP11(F(6)A2B) was more abundant in vulnerable rats, while most behavioral correlations occurred in the prefrontal cortex. In conclusion, we found N-
glycans (especially PGP15(FA3G2)) in plasma as possible
biomarkers of vulnerability to
trauma that warrants further investigation. Posttrauma PGP17(A2G2S1) increase showed overlap with human results highlighting the utility and relevance of this animal model. Prefrontal cortex is a key site of
trauma-induced glycosylation changes that could modulate the behavioral outcome.