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 towards 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.
