A team from the EPFL Brain Mind Institute has discovered an important synaptic mechanism: the activation of a cleaving enzyme, leading to behavioral problems connected to chronic stress.
Why is it that when people are too stressed they are often grouchy, grumpy, nasty, distracted or forgetful? 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 at EPFL discovered an important synaptic mechanism in the effects of chronic stress. It causes the massive release of glutamate which acts on NMDA receptors, essential for synaptic plasticity. These receptors activate MMP-9 enzymes which, like scissors, cut the nectin-3 cell adhesion proteins. This prevents them from playing their regulatory role, making subjects less sociable and causing cognitive impairment.
Carmen Sandi's team went to look for answers in a region of the hippocampus known for its involvement in behavior 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.
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.
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 subjectscould 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 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.
Carmen Sandi | Eurek Alert!
Win-win strategies for climate and food security
02.10.2017 | International Institute for Applied Systems Analysis (IIASA)
The personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research