Amandine Fernandez, Camille Dumon, Damien Guimond, Roman Tyzio, Paolo Bonifazi, Natalia Lozovaya, Nail Burnashev, Diana C Ferrari, Yehezkel Ben-Ari; The GABA Developmental Shift Is Abolished by Maternal Immune Activation Already at Birth, Cerebral Cortex, novembre 2018
Maternal Immune Activation (MIA) is due to an intrauterine infection that perturbs the immune system leading to the release of various inflammatory molecules that impact brain development. MIA is associated with neurodevelopmental disorders and notably Autism Spectrum Disorders (ASD) in offspring in both humans and animal models. Extensive investigations suggest that the infection leads to long term deleterious sequels and recent studies suggest that this is associated with cortical malformations. However, whether early developmental stages and notably the delivery and birth process are impacted are not known. In earlier studies, we showed that ASD is associated with an abolition of the oxytocin mediated neuroprotective GABA excitatory /Inhibitory shift leading to excitatory actions of GABA that persist in young adults. Somehow the polarity of GABA at birth is instrumental in the long term deleterious sequels of intrauterine insults. We now report that similar alterations occur at birth in MIA treated pregnant mice: the offspring have deficiencies already at birth. The oxytocin mediated neuroprotective GABA excitatory /Inhibitory shift that takes place at birth is alleviated suggesting that MIA impacts the process of birth. This is to the best of our knowledge the first demonstration that MIA impacts delivery stressing the need to better investigate the mechanisms that operate at birth and how they are impacted by intrauterine insults. Interestingly, neurons are also more arborized at birth after MIA suggesting that neuronal growth process is affected during labour and birth and neurons continue growing during these two events. There are a number of likely suspects and notably BDNF that is activated by excitatory GABA and calcium rise and the concentration of which is increased in children with ASD. This study calls for better determination of the conditions at which labour and parturition occur after an intrauterine insult. It also has implications on the possible links between insults that will lead to ASD and other developmental disorders and preterm delivery; clearly these types of studies are central in relation to topics of wide public health interest considering the increased incidence of both preterm delivery and ASD.