Epigenetics and the Oxytocin Pathway

Completed

Connelly, Jessica

University of Virginia

$119,999.00

2 years

Pilot

Charlottesville

VA

United States

2010

http://www.virginia.edu

City: 
Charlottesville
State/Province: 
VA
State/Province Full: 
Virginia
Country: 
United States

Autism spectrum disorders (ASD) are first seen in early life and may be in part based on genetic vulnerability. The neuropeptide oxytocin (OT) has been recently implicated in both positive social behaviors and the regulation of anxiety and emotion. Some clinicians have recommended OT treatments for ASD, in spite of the fact that the mechanisms, through which OT acts, especially during development, remain poorly understood. It is critical to gain a deeper understanding of the factors that regulate the production and actions of OT, since it is possible that inappropriately used treatments could do harm. It has been shown that the expression and effects of several important genes involved in ASD, including those that regulate OT, can be influenced by early experience. This research project capitalizes on a recent collaboration between a young scientist with expertise in genetics, genomics and epigenetics and an experienced neuroscientist (C. Sue Carter) who is a pioneer in the study of behavioral effects of OT. Recently, the Principal Investigator discovered that ASD genome is more heavily methylated at the gene for the OT receptor (OXTR), which coincides with decreased expression of the OXTR gene. This exciting finding is highly consistent with other recent sources of evidence implicating OT and the gene for the OT receptor in ASD, and also suggesting that the behavioral and neural systems at the core of ASD can be affected epigenetically by experience. Evidence from the collaboration suggests that relatively small changes in early life can alter the expression of the features of ASD, including social behavior and anxiety. This study further develops these animal models by testing the role of specific experiences in the first week of life in the epigenetic programming of the genes for OT and its receptor as well as, AVP and its receptor. Dr. Carter's lab has used these models to uncover an optimistic finding that developmental exposure to OT can reverse some of the effects of adverse early experiences. The same genes will be tested for epigenetic changes that occur with OT treatment early on and OT treatment during labor. Availability of this model will allow future experiments on ways to protect against or reverse the adverse effects of early experience, which will in turn improve our understanding of the behavioral and emotional features of ASD and thus suggest ways to identify risks for ASD, and eventually prevent and treat children with this disorder.