Study Explains Why Stress Makes People Dumb, Asocial

Stress lowers test performance and causes mood swings and even forgetfulness. A new study explains why stressful people act grouchy and distracted.

Brain Mind Institute (BMI) at Ecole Polytechnique Federale de Lausanne scientists report that they have found the mechanism behind chronic stress and the loss of social and cognitive skills. The research shows that stress affects brain performance at molecular level.

The team says that an enzyme called MMP-9 attacks a synaptic regulatory molecule in the hippocampus region of the brain. Breakdown of these molecules leads to stress-related symptoms.

Nectin-3 cell adhesion protein in a region within the hippocampus ensures adherence between two neurons. The researchers found that animal models that were chronically stressed had lower levels of nectin-3 molecule.

Further investigation revealed that an enzyme called MMP-9 was cutting these protein molecules.

Previous research has shown that long-term stress leads to high levels of glutamate, which affects NMDA receptors. Synaptic plasticity is highly dependent on NMDA receptors. So, their absence affects the stability of these connections and in turn, affects memory and thinking. The latest research shows another enzyme-related mechanism that causes cognitive impairments.

"When this happens, nectin-3 becomes unable to perform its role as a modulator of synaptic plasticity" explained Carmen Sandi from Brain Mind Institute (BMI) at EPFL. This change at molecular level causes a decrease in sociability, memory and thinking.

The current study was conducted on rat models. The researchers tweaked levels of nectin-3 or inhibited MMP-9 in their brains. The team was able to demonstrate that altering activity of these two molecules was enough to change mood and behavior of the animal.

"The identification of this mechanism is important because it suggests potential treatments for neuropsychiatric disorders related to chronic stress, particularly depression," said Carmen Sandi in a news release.

What's more, the researchers already know that MMP-9 is associated with other brain diseases such as ALS or epilepsy. The current study shows that other neuroscientists might consider targeting the enzyme to develop treatments for neurodegenerative diseases.

The study is published in the journal Nature Communication.