Neuronal deficits in the unborn due to maternal infection: the novelties in a study by In-CNR and Humanitas

A study by the Institute of Neuroscience of the National Research Council (In-CNR) and Humanitas, published in Biological Psychiatry, sheds new light on some molecular mechanisms responsible for defects in the development of the brain of the unborn child, as a result of activation of the maternal immune system.

“The association between maternal infections during pregnancy and neurodevelopmental defects of the unborn child has long been known, but the molecular mechanisms underlying this process are not yet clear. In our study carried out on mouse models, using an agent (PolyI:C) that mimics a viral infection, we showed that a single activation of the maternal immune system, in the early stages of pregnancy, makes the offspring more susceptible to the onset of epileptic seizures,” explains Professor Michela Matteoli, director of In-CNR and Head of the Neuro Center of Humanitas. “The main novelty of the work consists in the demonstration that this effect is mediated by an unbalance of the expression of two proteins, Nkcc1 and Kcc2”. An imbalance in the expression of these proteins prevents the Gaba neurotransmitter from acquiring its physiological inhibitory action. Excessive neuronal excitation, caused by the lack of the Gaba inhibitory brake, generates abnormalities in the nervous system, as in epilepsy and other neurodevelopmental diseases.

 

The rise of inflammatory cytokines

“Our work shows that an imbalance in the expression of the two proteins can be caused by the increase in inflammatory cytokines that occurs in the fetal brain following maternal infection,” adds Davide Pozzi, researcher at Humanitas University and co-author of the study. A possible therapy was tested within the study. “Pre-treatment of the mother with magnesium sulphate, which blocks the increase of inflammatory cytokines in the fetal brain following activation of the maternal immune system, prevents the harmful effects of infection. The data are very encouraging, although studies on pregnant women are necessary to unequivocally confirm the usefulness of this therapy,” concludes Professor Matteoli.