CONSEGUENZE DELL¿ATTIVAZIONE IMMUNITARIA MATERNA SULLO SVILUPPO NEUROLOGICO DELLA PROLE

Accumulating evidence indicate that immune deregulation or inflammation are linked to several types of psychiatric diseases (Patterson, 2009). Accordingly, perinatal infections have been associated with increased risk for neurodevelopmental disorders (Boksa, 2010; Meyer et al., 2006), including schizophrenia (Miller, Culpepper, Rapaport, & Buckley, 2013), autism (Shi, Fatemi, Sidwell, & Patterson, 2003) and epilepsy (Pineda et al., 2014). By using the POLY I:C (polyinosinic-polycytidylic acid) model of inflammation, we addressed the possibility that a single inflammatory event during pregnancy may alter neurodevelopmental processes, thus leading to neurologic disorders in the offspring. Our results demonstrate that a single injection of POLY I:C at gestation day 9 causes higher susceptibility to kainate-induced seizures in the offspring and other behavioral aberrations. This is associated with increased permeability of the Blood-Brain Barrier (BBB), due to alterations in tight junctions, as demonstrated by a reduction of Claudin-5 expression levels. The inflammatory status of adult animals doesn’t represent a susceptibility factor; only early alterations are visible. No changes in microbiota was observed in the offspring of POLY I:C-treated mothers. Wnt/β-catenin pathway and pericytes markers alterations are instead had found both in developmental and adult stages of POLY I:C-treated mothers offspring. Our results thus open to the possibility that inflammation during early pregnancy may increase susceptibility to psychiatric diseases and epilepsy by interfering with normal brain vascularization and BBB formation.