Microglia in Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Florida
Investigators Name
Streit, Wolfgang J., PhD

Little is known about the neuropathology underlying Tourette syndrome. In this proposal, we will attempt to uncover novel histopathological features of Tourette syndrome (TS) that could further illuminate the pathogenesis of this condition. Specifically, we plan to perform an in-depth investigation of microglial cells since there are no published studies on this subject. Microglia are known to be very sensitive cellular indicators of neuronal malfunctioning, and thus our working hypothesis that microglial reactivity can identify and define previously unrecognized patterns of cellular pathology in TS brain. We will perform neuro-histopathological studies using human brain samples from both control subjects and from subjects with TS to delineate distributions of both activated and dystrophic microglia. Detection of activated microglia will serve to identify sites of neuroinflammation while presence of dystrophic microglia will likely coincide with sites of chronic neurodegeneration, such as tau or ?-synuclein pathology. Double immunohistochemistry for microglia and neuronal markers (hyperphosphorylated tau, ?-synuclein, dopamine transporter) will be employed to investigate microglial-neuronal relationships in TS. Thus, our objectives will be two-fold: 1) to establish presence/absence of activated and/or dystrophic microglia; 2) to identify sites of neuronal degeneration. Our laboratory has been studying microglia in the diseased human and animal central nervous system for twenty-five years, and we have developed a standard panel of immunohistochemical markers that, together with high resolution morphological assessment of microglia, will allow us to reliably discriminate the various forms of these cells. Overall these studies are expected to provide new insight into the pathogenetic mechanisms underlying TS. Wolfgang J. Streit, Ph.D. & Quig-shan Xue, Ph.D. University of Florida College of Medicine, Gainesville, FL Award: $75,000 Tourette Association of America Inc. – Research Grant Award 2013-2014