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Activation of MMP-9 enzyme (Involved in ALS, Epilepsy) leads to behavioral problems connected to chronic stress

Activation of MMP-9 enzyme (Involved in ALS, Epilepsy) leads to behavioral problems connected to chronic stress

stressA 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 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 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.

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