Immunocytochemical Localization of Dyskinesia -Inducing Tourette IgG in the Striatum

Grant Type
Basic
Grant Year
2001-2002
Institution Location
RI
Institution Organization Name
Brown University
Investigators Name
Hallett, Joseph, MD

Our group has shown that serum antibodies (TSIgG) will cause stereotypies when infused into the striatum of rats. When these brains were examined, the antibodies were found to be bound to neurons in the lateral striatum. In a pilot study we demonstrated that TSIgG bound to neurons also contained substance P. In the currently accepted model of striatal organization, substance P and dopamine D1 receptors are found on the same neurons and these neurons are a major component of the basal ganglia’s indirect pathways. This finding is of interest because pharmacologic and neuroimaging studies suggest that neurons expressing dopamine receptors have an important role in the expression of tics in TS. Moreover, axon-mapping studies in rats show that the lateral striatum receives projections from cortical motor neurons that control forelimb, head and facial movements. These are the same movements that become dyskinetic when TS-IgG are infused into the lateral striatum of the animals. This proposal will extend our preliminary study by immunocytochemically characterizing the dyskinesia-inducing TSIgG binding in the striatum. More specifically, it will determine whether or not TSIgG selectively binds to neurons of the direct pathway in the lateral striatum, that is to neurons co-expressing substance P and dopamine D1 receptors. If selective binding to neurons in the direct pathway is found this would suggest a possible pathogenic mechanism by which anti-neuronal antibodies from TS sera could alter basal ganglia function, which in turn results in these stereotypic behaviors. These data may also suggest new therapeutic approaches to treating Tourette syndrome. Joseph H. Hallet, M.D. Brown University of Medicine/Memorial Hospital of Rhode Island, Pawtucket, RI Award: $72,749 Tourette Association of America Inc. – Research Grant Award 2001-2002