Neuroanatomical Correlates of Tourette Syndrome lgG Induced Dyskinesias in Rats

Grant Type
Grant Year
Institution Location
Institution Organization Name
Memorial Hospital of Rhode Island
Investigators Name
Hallett, Joseph, MD

The mechanisms(s) for the initial expression of Tourette Syndrome (TS) and for its symptom exacerbation are not known. We have postulated that in some children the immune system plays a role in the pathogenesis of TS. The immune system can be divided into two parts, cellular immunity and humoral (antibody) immunity. We have directed our efforts at investigating the possible role of antibodies in TS. The involvement of antibodies is not an unexpected finding because immune factors are known to be associated with other central nervous system disorders. A recent family study suggests that the occurance of TS may be the result of an interaction between genetic and environmental factors. It was estimated that environmental factors may contribute to as many as 62% of the TS cases. However, this study provided no data on the specific environmental factors that might be involved. Past studies have found that a significant number of children with movement disorders (including TS) had antibodies in their blood that bound to the basal ganglia, a structure in the brain believed to play a central role in causing tics. One explanation for the presence of these antibodies is that they were synthesized in response to an environmental agent. We have hypothesized that these antibodies are involved in TS symptom expression. Previously, we showed that an injection of dilute TS sera containing antibodies into a rat’s basal ganglia induces dyskinesias (involuntary movements). The movements observed were stereotypic, and can be viewed as analogous to tics in humans. Also, these movements can be induced by drugs that interfere with the dopamine system of the brain (This system is important to TS research because medications commonly used in the treatment of TS alter dopamine levels in the brain.) In addition to the dyskinesias, episodes of brief, high to moderately pitched sounds were heard from these rats. Similar sounds were not heard from rats infused with the sera from children without TS. In a preliminary study, the brain of a rat that was infused with TS serum was examined with immunohistochemical techniques to determine whether serum antibodies bound to brain tissue. Inspection of brain sections revealed that antibodies were selectively binding to large neurons in the striatal region of the basal ganglia. We found no binding in another rat that was infused with serum from children without TS. This antibody binding may represent a neural mechanism by which antibodies cause dyskinesias. This study will test other TS sera in rats to determine if a similar pattern of antibody binding in the basal ganglia occurs. A demonstration of selective binding to neurons in the basal ganglia would suggest a mechanism by which an environmental factor can participate in the expression of TS. It also would suggest a new approach to treatment. Joseph J. Hallett, M.D., Edward G. Stoppa, M.D., Christine J. Harling-Berg, Ph.D,. Louise S. Kiessling, M.D. Memorial Hospital of Rhode Island Pawtucket, RI Award: $40,255 Tourette Association of America Inc. – Research Grant Award 1997