Abstract

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.

摘要

创伤后应激障碍（PTSD）是由10–20％的暴露对象的创伤事件触发的。通过修饰蛋白质功能，N-联糖基化可提供重要的环境关联性预测脆弱性。我们的目标是（1）寻找血浆N-糖蛋白的变化，预测应激的脆弱性；（2）研究创伤如何影响血浆（PGP）和三个与PTSD相关的大脑区域（前额叶皮层，海马和杏仁核； BGP）中的N-糖基，从而揭示PTSD治疗的具体靶标。我们检查了雄性（1）对照组，（2）受电击的脆弱大鼠和（3）受电击的弹性大鼠在电击前和电击后数周。弱势群体和弹性群体之间用z分隔行为的得分分析。与对照组和有复原力的大鼠相比，在脆弱人群中发现了更高的冰冻行为和社会兴趣降低。先天性焦虑并不能预示其脆弱性，但创伤前PGP10（FA1G1Ga1），PGP11（FA2G2）和PGP15（FA3G2）的水平与其呈正相关，最后一个最为敏感。创伤性应激在所有受创伤动物的血浆中，尤其是在易感大鼠的前额叶皮层中，导致从大型的复杂N聚糖向较简单的中性结构转变。在血浆创伤中，脆弱动物的PGP17（A2G2S）水平升高。在所有三个大脑区域中，BGP11（F（6）A2B）在易感大鼠中更为丰富，而大多数行为相关性发生在前额叶皮层中。结论，我们发现血浆中的N-聚糖（尤其是PGP15（FA3G2））可能是易受创伤的生物标志物，值得进一步研究。创伤后PGP17（A2G2S1）增加显示与人类结果重叠，突显了该动物模型的实用性和相关性。前额叶皮层是创伤引起的糖基化变化的关键部位，其可能调节行为结果。