Effects of Oxytocin Receptor Agonists in Mouse Models of Autism Spectrum Disorder Phenotypes
Beth Israel Deaconess Medical Center
Meixner Translational Postdoctoral Fellowship
There are no drug treatments available to alleviate the social deficits associated with autism spectrum disorders (ASDs). However, nasal spray administration of the prosocial hormone oxytocin (OT) improves social deficits in ASD patients and thus appears to be a possible option for ASD treatment. Unfortunately, OT as a drug suffers from two drawbacks because it is unstable in the body and has poor entry into the brain from the bloodstream. In order to develop OT-related drugs that overcome these challenges, mouse models of ASD-like behavior are needed to test if drug candidates might be effective treatments for human ASDs. Towards this goal, the study evaluates the ability of OT and an OT-related drug (Cmpd 39) to reduce the social deficits exhibited by three strains of mice, BALB/cByJ, C58/J, and Grin1 mutant, which are ASD-like mouse models developed by the research team. If these drug treatments are successful, it would demonstrate that these models are scientifically relevant for ASD drug discovery and that OT-related drugs may be effective in treating human ASDs. Another challenge of developing OT-related drugs is that there is very little known about the ways in which OT is able to promote social behavior in mammals. One way that OT works is by turning on or off genes, but the identities of these genes in the brain are unknown. Using a method called microarray, the researchers will assess how OT treatment in ASD-like mouse models changes the expression of genes in brain regions important for social behavior. This information could allow for the development of highly specific OT-related drugs, which may have fewer side effects, and advance our understanding of ASDs and how to treat them. The goal of the training is to provide the fellow with diverse learning and practical experiences in multiple aspects of ASD research and drug discovery. There will be three main components of training, which include the following: 1) mouse behavioral phenotyping, 2) OT molecular biology, and 3) human ASD clinical studies. The fellow aims to acquire the knowledge and translational skills necessary to integrate basic and clinical research paradigms that accelerate the development of effective therapies for ASDs.