Loss of social skills
Researchers from the Brain Mind Institute (BMI) at EPFL 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. This was revealed by a work published in Nature Communications.
Carmen Sandi's team went to look for answers in a
region of the hippocampus known for its involvement in behaviour and cognitive
skills. In there, 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.
Read: The symptoms of stress
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 which, 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 Carmen Sandi. In turn, these effects lead subjects to lose their
sociability, avoid interactions with their peers and have impaired memory or
understanding.
Potential treatments
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.
Read: Managing stress
"The identification of this
mechanism is important because it suggests potential treatments for
neuropsychiatric disorders related to chronic stress, particularly
depression," said Carmen Sandi, member of the NCCR-Synapsy, which studies
the neurobiological roots of psychiatric disorders.
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," concluded Carmen Sandi, the BMI's
director.
Read more:
Understanding stress
Stressed out?
Ditch the stress
Image: Frustrated young man from Shutterstock