The people who can carry on amiable conversation while also fighting a war inside their heads are few and far between. When we get stressed, we shut down. We recede from the social sphere, if only to count to 10, before rejoining the group with a clearer frame of mind. But what, exactly, is going on between our ears when all this is happening?

New research from the Brain Mind Institute at École polytechnique fédérale de Lausanne (EPFL), in Switzerland, suggests the neural mechanism that makes stress a precursor to antisocial behavior happens at the synaptic level. Specifically, there is a disruption between a key enzyme and a set of proteins necessary for sociability. Keeping that relationship intact could open important doors for the treatment of psychiatric disorders.

There’s a type of protein whose main function in the brain is to keep neurons stuck together. They’re called adhesion proteins, and one in particular, the nectin-3 adhesion protein, has been found in prior research to play a vital role in the preservation of cognitive functions. In rats with chronic stress, researchers recently found nectin-3 levels were substantially lower.

In looking for possible causes of the decrease, the researchers ended up at the enzyme MMP-9, known for its role in protein degradation. What they found when they looked at MMP-9 activity in the brain was that during episodes of chronic stress, when the neurotransmitter glutamate is released, the receptors responsible for memory and synaptic plasticity activated MMP-9. Literally like scissors, the enzyme cut the nectin-3 proteins.

"When this happens, nectin-3 becomes unable to perform its role as a modulator of synaptic plasticity" explained lead author and Brain Mind Institute professor Carmen Sandi in a statement. The end result for the rats was decreased sociability, avoidant behavior, and impaired memory and understanding.

By contrast, when EPFL researchers and a team of Polish scientists tried to reverse the effect — in other words, boost sociability through nectin-3 restoration — they found in in vitro and in vivo models that these external treatments yielded positive effects. Cognitive skills improved and memory returned. "The identification of this mechanism is important because it suggests potential treatments for neuropsychiatric disorders related to chronic stress, particularly depression," Sandi said.

The research is admittedly early for any clinical application. So far, no drugs have been developed using nectin-3 as their primary target. Sandi and her team hope the findings can be repeated in future studies. Given the success with MMP-9, they also hope to exploit its benefits for other neurological diseases, like amyotrophic lateral sclerosis or epilepsy.

"This result opens new research avenues on the still unknown consequences of chronic stress,” Sandi said.

Source: Sandi C, et al. Nature Communications. 2014.