It’s Official – Stress Alters the Way Brain Proteins Are Glycosylated

We all know that too much stress is bad. It has detrimental consequences for nearly all aspects of our physical and mental health. It especially impacts areas such as immune function, mood, blood pressure, and cognition. But we have known for a long time that stress also affects protein glycosylation, the process of adding sugars onto proteins to modify their function or stability. Previous studies focused on the effect of stress on glycosylation of proteins found in the bloodstream (i.e. plasma proteins) and they established that chronic stress in the context of Post-Traumatic Stress Disorder (PTSD) causes changes in glycosylation that are similar to accelerated ageing.

But a recently published study has shown for the first time that traumatic stress also leads to long-lasting changes in the glycosylation of brain proteins. Using a rat model of PTSD, researchers studied the glycans attached to brain proteins to see whether their glycosylation was altered one month after the stressful event. Just as in humans, where only 10-20% of people who experience trauma go on to develop PTSD, exposure to a stressful stimulus triggered PTSD-like symptoms, such as anxiety and decreased social interest, in only a subset of rats (the ‘vulnerable’ group) while other rats did not display such symptoms despite experiencing the exact same treatment (the ‘resilient’ group).

Interestingly, stress only caused changes in brain glycosylation in the vulnerable group indicating that there is something peculiar about these animals that makes them susceptible to these types of changes when confronted with a stressful situation. The nature of the changes was similar to that observed for blood proteins, that is to say, in line with changes described for accelerated ageing.

But what was most interesting was that these changes were not observed throughout the whole brain. Rather, they only occurred in one specific brain region, the prefrontal cortex (PFC), which is the part of the brain responsible for decision making, executive function, and higher order cognition. This is not surprising since malfunctioning of the PFC has previously been implicated in PTSD. However, these findings have, for the first time, established a connection between stress-induced changes in PFC glycosylation and vulnerability to PTSD which suggests that disrupted brain glycosylation may play a role in PTSD pathology. For now, the implications of these changes for brain function are unknown, and more research is needed to address this. But one thing is clear – we can now add brain glycosylation to the long list of things affected by stress.