Our long-term goals are to understand the molecular and biochemical causes of Tourette syndrome (TS) and related disorders. This study will focus on the autoimmune hypothesis recently proposed as an etiology for Tourette syndrome and related disorders. The hypothesis predicts that antibodies against group A b-hemolytic streptococci cross-react with neuronal proteins in the brain and produce alterations in neuronal function. Recent work has established that autoantibodies exist in the sera of a subset of patients with these disorders. We will attempt to develop and validate an animal model for these disorders by infusing autoantibodies from patients with TS into the brain of rodents. Sera or affinity purified antibodies (IgGs) will be infused into the ventrolateral (VL) or ventromedial (VM) striatum in an effort to reproduce symptoms of the disorder. We will monitor stereotypies and vocalizations through video-audio taping to quantify these behavioral changes. Sera from several control groups (in addition to material from TS patients) with autoantibodies will be studied. Also, sera from TS patients with no autoantibodies present will be infused in addition to samples from normal control subjects. Our preliminary data suggest that infusions of sera from TS patients into the VL produces oral stereotypy and alterations in behavior. We predict that stress will exacerbate stereotyped behavior in our experimental animals. We also propose to investigate whether animals show alterations in reward-related learning and impulsivity. Although motor and phonic tics constitute the core of diagnostic elements of TS, patients frequently have attentional problems, learning deficits, disinhibition, and obsessive compulsive symptoms. We hypothesize that infusions of sera or IgGs will produce alterations in these behaviors in our experimental animals. The development of a valid animal model for TS is critical as it will allow investigators to explore the underlying disruptions to normal neuronal function that occur in TS, and thus lead to investigation of novel therapeutic interventions. Jane Rebecca Taylor, Ph.D. Yale School of Medicine, New Haven, CT Award: $53,815 * This study has been underwritten through a generous contribution from the William F. Harnisch Foundation. Tourette Association of America Inc. – Research Grant Award 2001-2002