Animal models recapitulating the multifactorial origin of Tourette syndrome

Abstract

Tourette Syndrome (TS) is a neurological disorder characterized by motor and phonic tics affecting approximately 1% of the pediatric population. Behavioral comorbidities often include obsessive-compulsive behavior and impaired attention. The neurobiological substrates associated with TS generally entail abnormalities in neurotransmitter circuitry regulating basal ganglia activity. The neurotransmitters most often associated with TS are dopamine, serotonin, and GABA. TS origin roots in genetic predisposing factors, and environmental variables favoring tic onset and exacerbation. Among the latter, repeated infections with group A beta-hemolytic Streptococcus and psychosocial stressors encountered during development have been proposed to constitute likely susceptibility factors. In this chapter, we describe how this clinical/epidemiological knowledge has been translated into animal models of TS. Specifically, we review several studies attempting to reproduce TS-like symptoms (tics and behavioral stereotypies) and comorbidities (impaired attention, increased locomotion, and perseverative responding) in laboratory rodents. Additionally, we discuss studies in which the genetic and environmental predisposing factors have been modeled in experimental subjects. Ultimately, we propose a unifying perspective recapitulating dependent and independent variables in the preclinical study of TS and discuss its potential theoretical and heuristic implications.

Keywords: Autoimmunity; Environment; Genetics; PANDAS; Rodents; Tic disorders.