Is Stress Eating Away at You? No, Literally…
Ever wonder why, when people are too stressed, they are often grouchy, grumpy, nasty, distracted or forgetful? It may not be something you’ve done, in fact it turns out stress is literally tearing apart the brain. By this I mean that researchers have just highlighted a fundamental synaptic mechanism that explains the relationship between chronic stress and the loss of social skills and cognitive impairment. When triggered by stress, an enzyme attacks a synaptic regulatory molecule in the brain. In other words, when people use the colloquialism “what’s eating you?” the answer might just be, stress.
The research team went to look for answers in a region of the hippocampus known for its involvement in behavior and cognitive skills. Scientists were interested in a molecule, the nectin-3 cell adhesion protein, whose role is to ensure adherence, at the synaptic level, between two neurons. Positioned in the postsynaptic part, these proteins bind to the molecules of the presynaptic portion, thus ensuring the synaptic function. However, the researchers found that on rat models affected by chronic stress, nectin-3 molecules were significantly reduced in number.
The investigations conducted by the researchers led them to an enzyme involved in the process of protein degradation: MMP-9. It was already known that chronic stress causes a massive release of glutamate, a molecule that acts on NMDA receptors, which are essential for synaptic plasticity and thus for memory. What these researchers found now is that these receptors activated the MMP-9 enzymes — for those who didn’t click the link these enzymes, like scissors, literally cut the nectin-3 cell adhesion proteins.
“When this happens, nectin-3 becomes unable to perform its role as a modulator of synaptic plasticity” explained Professor Carmen Sandi member of the NCCR-Synapsy, which studies the neurobiological roots of psychiatric disorders.
Because of these effects. subjects start to lose their sociability, avoid interactions with their peers and have impaired memory or understanding.
The team (in conjunction with Polish neuroscientists, go collaboration) were able to confirm this mechanism in rodents both in vitro and in vivo. By means of external treatments that either activated nectin-3 or inhibited MMP-9, they showed that stressed subjects could regain their sociability and normal cognitive skills.
“The identification of this mechanism is important because it suggests potential treatments for neuropsychiatric disorders related to chronic stress, particularly depression,” said Professor Sandi.
Interestingly, MMP-9 expression is also involved in other pathologies, such as neurodegenerative diseases, including ALS or epilepsy.
“This result opens new research avenues on the still unknown consequences of chronic stress,” Professor Sandi said.
The news might not be that surprising when you look at children (or adults) who came from abusive homes or veterans who typically come home from war and seem disconnected from society. Unfortunately the team has no real idea on how to treat the problem, so while now when you are not feeling too sociable you have a pretty good excuse, you don’t have a reliable way to undo the damage… yet.
In any case knowing the mechanism that causes the problem is just shy of being able to fix it.
van der Kooij, M., Fantin, M., Rejmak, E., Grosse, J., Zanoletti, O., Fournier, C., Ganguly, K., Kalita, K., Kaczmarek, L., & Sandi, C. (2014). Role for MMP-9 in stress-induced downregulation of nectin-3 in hippocampal CA1 and associated behavioural alterations Nature Communications, 5 DOI: 10.1038/ncomms5995