Oxytocin seals the blood-brain barrier, improving 22q11.2 deletion syndrome trajectories

Abstract

Understanding the connection between genetic susceptibility and immune alterations in neurodevelopmental disorders remains limited. Here, we investigated the 22q11.2 hemideletion syndrome (22q11.2DS), a prominent genetic risk factor for psychiatric disorders, focusing on its interaction with immune alterations. Using the 22q11.2DS mouse model LgDel/+, we identified adolescence as a critical period for the emergence of behavioural and cortical anomalies, associated with peripheral regulatory T cell reduction, microglial inflammatory activation and cerebral myeloid cell infiltration. Neonatal intranasal oxytocin supplementation prevented the appearance of sensorimotor gating, social behaviour and immune system deficits in 22q11.2DS mice. This was related to an early and long-lasting effect of oxytocin in upregulating tight junction molecules claudin-5 and claudin-1, with claudin-5 leading to reduced permeability of the blood-brain barrier. Consequently, myeloid cell infiltration into the brains of 22q11.2DS mice was reduced. Our findings elucidate a genetic-immune interplay in the aberrant development associated with 22q11.2DS, supporting a novel therapeutic potential for oxytocin in sealing a critical brain barrier.

Keywords: 22q11.2 deletion syndrome; blood–brain barrier; claudin-5; immune system; oxytocin.