Improving developmental trajectories in 22q11.2 deletion syndrome by oxytocin: focus on anti-inflammatory effects

Objectives and aims. The objective of this project is to implement, in a biologically-supported way, an intranasal oxytocin (OXT) treatment to ameliorate the still incurable social, cognitive and immune system deficits characterizing the 22q11.2 microdeletion syndrome (22q11.2DS). Specifically, we will identify the selective behavioral domains, as well as the central and peripheral immune system components ameliorated by perinatal or adolescent exposure to OXT in the LgDel/+ 22q11.2DS mouse model. Then, we will disentangle the specific brain-immune connections involved in the rescue process. Background/Rationale. Our preliminary evidence indicates that in 22q11.2DS mice, which embed the well conserved full hemideletion found in 22q11.2DS patients, OXT exposure might ameliorates some social and immune developmental trajectories. However, the extend of the ameliorative effects in other social, cognitive and immune system deficits, as well as the role played by the brain-immune interconnections in the mechanisms of rescue is unknown. Research design and methods. Using LgDel/+ mice, we will first comprehensively characterize the behavioral and immune system consequences of OXT. We will use state-of-the-art behavioral assays, with proved validity to the clinics, as well as a series of in-depth assessments of the functionality of both the peripheral and central immune system. Next, to sort OXT-dependent mechanisms, we will manipulate selective immune system components at the peripheral or central levels, checking for peripheral-brain immune communication. Anticipated output. Establish a new strategy to correct altered developmental trajectories in 22q11.2DS, at the same time providing new knowledge on OXT neuroimmunomodulatory effects and immune-brain communication as the base of psychiatric-relevant phenotypes and treatments.