Vulnerability to stress is associated with alterations in N-glycosylation in the blood and brain

Autor: Fazekas, Csilla, Sipos, Eszter, Klarić, Thomas Stephen, Török, Bibiána, Bellardie, Manon, Erjave, Gordana, Lauc, Gordan, Pivac, Nela, Zelena, Dóra
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Popis: Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder triggered by exposure to traumatic events and occurs in 10-20% of exposed subjects. The molecular mechanisms contributing to PTSD pathology are poorly understood. N-linked glycosylation, by modifying protein function, may modulate an animal’s behavioural response in the context of traumatic stress. Here we used a rat foot-shock model of PTSD to investigate the impact of traumatic stress on N-glycosylation in three PTSD-related brain regions (prefrontal cortex [PFC], hippocampus, and amygdala), as well as blood which was taken both pretrauma and 26 days after trauma. We used z-score, a metric combining data from several behavioural tests, to segregate animals into vulnerable and resilient groups to identify differences in N-glycosylation in these subpopulations. In the brain, vulnerable rats showed divergent N-glycosylation only in the PFC. Greater vulnerability to stress was associated with a shift in N-glycosylation from large, elaborate N-glycans towards simpler, neutral structures in the PFC. In the blood, trauma caused long-lasting changes in plasma protein N- glycosylation with the general trend being a shift from sialylated N-glycans towards neutral complex structures. Yet these changes were not uniform for all animals. Rather, the changes were modulated by the animal’s underlying vulnerability to stress. Changes in the abundance of specific N-glycan structures were observed that were unique to either the vulnerable or resilient group indicating that alterations in N-glycosylation arising from trauma manifest differently in animals with varying predispositions to stress. In pretrauma blood, three N-glycan peaks containing neutral complex structures were found to correlate positively with stress vulnerability making them promising biomarker candidates. Overall, these findings demonstrate that vulnerability to stress is associated with alterations in N-glycosylation in both the PFC and blood.
Databáze: OpenAIRE