Possible Neuropathology Underlying TS: An Immuno-histochemical Study of the Striatopallidal Projection System

Grant Type
Basic
Grant Year
1990
Institution Location
TN
Institution Organization Name
University of Tennessee
Investigators Name
Reiner, Anton, PhD

The rationale for the studies we want to carry out on Tourette Syndrome (TS) derives from our recent studies on the neuropathology underlying the involuntary movements observed in the early stages of Huntington’s disease (HD). We believe these studies provide some significant clues as to the possible neuropathology underlying TS. Specifically, our HD studies show that the choreiform (hyperkinetic) movements characterizing the early stages are associated with a loss of enkephalinergic striatopallidal projection neurons. Since these HD symptoms can be ameliorated by blockade of dopaminergic transmission and exacerbated by administration of dopaminergic agonists (as can TS symptoms), and since HD is a disorder involving an inability to suppress unwanted movements (as is also true of TS), we believe it possible that the neural disturbance in TS affects the same neuronal population as affected in early HD. Specifically, we hypothesize that TS is caused by a focal hypofunction of those enkephalinergic striatopallidal neurons that are responsible for suppressing the involuntary TS movements. To explore this possibility, we plan to use immunohistochemical techniques on postmortem material from TS patients to determine whether there is a focal reduction in the number or staining intensity of enkephalinergic striatopallidal terminals in the lateral globus pallidus. Since these terminals co-contain both GABA and enkephalin, we will use immunohistochemical techniques using antisera against enkephalin and glutamic acid decarboxylase (GAD), the synthetic enzyme for GABA, to label alternate sections. Since the deficit is likely to be localized and subtle, for each case we will examine a series of sections throughout the entire extent of the pallidum and we will use computer-assisted image analysis techniques to quantify the extent of loss in comparison to normal individuals. In addition, we will use antisera against substance P to label the striatonigral projection system and the projection to the medial part of the globus pallidus and examine the integrity of these projection systems in TS specimens. If our hypothesis proves correct, future studies could focus on determining the nature of the defect that leads to hypoactivity of the affected population of striatal neurons projecting to the lateral globus pallidus. Anton Reiner, Ph.D. University of Tennessee, Memphis, TN Award $25,000 Tourette Association of America Inc. – Research Grant Award 1990