A new study has revealed how chronic stress leads to behavioural problems in people.
Researchers from the Brain Mind Institute (BMI) at EPFL have 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.
Carmen Sandi's team went to look for answers in a region of the hippocampus known for its involvement in behavior and cognitive skills. The investigations conducted by the researchers led them to an enzyme involved in the process of protein degradation: MMP-9. It was 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. The researchers found that these receptors activated the MMP-9 enzymes which 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 Carmen Sandi. In turn, these effects lead subjects to lose their sociability, avoid interactions with their peers and have impaired memory or understanding.
The researchers, in conjunction with Polish neuroscientists, 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 study is published in Nature Communications.
