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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.
Michael A. van der Kooij, Martina Fantin, Emilia Rejmak, Jocelyn Grosse, Olivia Zanoletti, Celine Fournier, Krishnendu Ganguly, Katarzyna Kalita, Leszek Kaczmarek, Carmen Sandi. Role for MMP-9 in stress-induced downregulation of nectin-3 in hippocampal CA1 and associated behavioural alterations. Nature Communications, 2014; 5: 4995 DOI: 10.1038/ncomms5995
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. Credit: EPFL
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