An Animal Model of Tourette’s Syndrome

Taylor, Jane R.; Morshed, Syed A.; Parveen, Salina; Mercadante, Marcos T.; Scahill, Lawrence; Peterson, Bradley S.; King, Robert A.; Leckman, James F.; Lombroso, Paul J.

doi:10.1176/appi.ajp.159.4.657

Cited by 125 publications

(83 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our results suggest that tics may relate specifically to deficits in the lateral/sensorimotor striatum and not to those in the more medial, associative circuitry. This is consistent with the role of the DLS in stereotypy and in habit learning in other contexts (20)(21)(22)41), and with findings of increased functional connectivity in the putamen to correlate with tic complexity (23). It is possible that dorsomedial pathology relates to other aspects of pathology, such as obsessive-compulsive symptoms (23), that are not readily captured by our behavioral assays in mice.…”

Section: Discussionsupporting

confidence: 86%

“…Whereas the cellular architecture of the dorsal striatum is fairly uniform throughout its medial-lateral extent, the topographic organization of cortical afferents leads to functional segregation among subregions (16)(17)(18)(19). The dorsolateral striatum (DLS), which corresponds roughly to the human putamen, has been associated with sensorimotor habits (20) and with tic-like stereotypies in rodents (21,22). Functional neuroimaging has correlated abnormalities in these lateral corticostriatal networks with tic characteristics in patients with TS, whereas abnormalities in medial networks correlated instead with comorbid obsessive-compulsive symptoms (23).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

Xu¹,

Kobets²,

Du³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

140

158

View full text Add to dashboard Cite

Gilles de la Tourette syndrome (TS) is characterized by tics, which are transiently worsened by stress, acute administration of dopaminergic drugs, and by subtle deficits in motor coordination and sensorimotor gating. It represents the most severe end of a spectrum of tic disorders that, in aggregate, affect ∼5% of the population. Available treatments are frequently inadequate, and the pathophysiology is poorly understood. Postmortem studies have revealed a reduction in specific striatal interneurons, including the large cholinergic interneurons, in severe disease. We tested the hypothesis that this deficit is sufficient to produce aspects of the phenomenology of TS, using a strategy for targeted, specific cell ablation in mice. We achieved ∼50% ablation of the cholinergic interneurons of the striatum, recapitulating the deficit observed in patients postmortem, without any effect on GABAergic markers or on parvalbuminexpressing fast-spiking interneurons. Interneuron ablation in the dorsolateral striatum (DLS), corresponding roughly to the human putamen, led to tic-like stereotypies after either acute stress or D-amphetamine challenge; ablation in the dorsomedial striatum, in contrast, did not. DLS interneuron ablation also led to a deficit in coordination on the rotorod, but not to any abnormalities in prepulse inhibition, a measure of sensorimotor gating. These results support the causal sufficiency of cholinergic interneuron deficits in the DLS to produce some, but not all, of the characteristic symptoms of TS.Tourette sydrome | basal ganglia | interneurons | acetylcholine | animal models

show abstract

Section: Discussionsupporting

confidence: 86%

mentioning

confidence: 99%

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

Xu¹,

Kobets²,

Du³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

140

158

View full text Add to dashboard Cite

show abstract

“…To explore the role of antibodies in the sera of TS patients, animal models of TS have been established in which the antibodies of TS patients are transferred into the brains of rats by microinfusion [15]. The involuntary movements seen in rats treated with intrastriatal microinfusions of TS sera or gamma immunoglobulins (IgG) are similar to those observed in TS.…”

Section: Discussionmentioning

confidence: 99%

“…Some case reports and cross-sectional studies have demonstrated the presence of antineuronal antibodies in patients with SC, tic disorders, and obsessive-compulsive disorder. It was thought that the autoantibody was induced by streptococcal infection, and that this antibody attacked the basal ganglion, resulting in the above mentioned neuropsychiatric symptoms [6,14,15]. Contrary to the above findings, several studies have investigated the controversial concept of PANDAS [5,7,[16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Antineural antibody in patients with Tourette’s syndrome and their family members

Yeh

Wu²,

Tsung³

et al. 2005

J Biomed Sci

Self Cite

View full text Add to dashboard Cite

SummaryIt has been proposed that antineural antibodies were present in patients with Tourette's syndrome (TS) and other neuropsychiatric disorders. The purpose of our study was to investigate the presence of antineural antibodies in the individuals with Tourette's syndrome and the family members of TS patients. The sera of four TS patients with no current streptococcal infection, their tic-free family members including father, mother and sibling, and a age-matched control group who were tic free were assayed for antineural antibodies directed against rat tissue and neurons in primary cell culture. There were prominent antineural antibodies present in TS patients and their first-degree family members, but not in the control group. Western blotting showed proteins of about 120 kDa in their sera that were not present in the sera of controls. The preliminary results of our study suggest the importance of genetic vulnerability in the immunological pathophysiology of tic disorders. Future studies should investigate the interactions of genetics, environment, infectious agents, and immunity on symptom expression in families with tic disorders.

show abstract

“…50 Several groups have reported the presence of antineuronal antibodies among patients with childhood-onset OCD and/or tic disorders. [51][52][53][54][55] Preliminary animal studies suggest these antineuronal antibodies may play an etiologic role in these neuropsychiatric disorders, [56][57][58] although there have been negative reports from investigators who were not able to induce behavioral changes through an infusion. 59 The striking effectiveness of immunomodulatory therapies, such as therapeutic plasma exchange and intravenous immunoglobulin (IVIG) in the PANDAS subgroup, suggests that there is systemic involvement, at least in severely affected individuals.61 Magnetic resonance imaging scans reveal enlargements of the caudate, putamen, and globus pallidus, which points to regional inflammatory changes, 60,61 while local autoimmune reactions are suggested by the presence of serum antibodies which cross-react with neurons of the caudate, putamen, and globus pallidus.…”

Section: Pathogenesis Of Pandasmentioning

confidence: 99%

PANDAS: current status and directions for research

2004

View full text Add to dashboard Cite

The recognition of the five criteria for PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) by Swedo et al established a homogenous subgroup of children with childhood onset obsessive-compulsive disorder (OCD) and/or tic disorders. The five clinical characteristics that define the PANDAS subgroup are the presence of OCD and/or tic disorder, prepubertal age of onset, abrupt onset and relapsing-remitting symptom course, association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity), and a temporal association between symptom exacerbations and a Group-A beta-hemolytic streptococcal (GAS) infection. These five criteria have been used for the purpose of systematic research on the phenomenology and unique therapies for the PANDAS subgroup as well as studies of the pathophysiology of poststreptococcal OCD and tic disorders. The etiology of OCD and tics in the PANDAS subgroup is unknown, but is theorized to occur as a result of post-streptococcal autoimmunity in a manner similar to that of Sydenham's chorea. The working hypothesis for the pathophysiology begins with a GAS infection in a susceptible host that incites the production of antibodies to GAS that crossreact with the cellular components of the basal ganglia, particularly in the caudate nucleus and putamen. The obsessions, compulsions, tics, and other neuropsychiatric symptoms seen in these children are postulated to arise from an interaction of these antibodies with neurons of the basal ganglia.

show abstract

An Animal Model of Tourette’s Syndrome

Abstract: The results are consistent with an autoimmune etiology in a subset of cases of Tourette's syndrome.

Cited by 125 publications

References 9 publications

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

Antineural antibody in patients with Tourette’s syndrome and their family members

PANDAS: current status and directions for research

Contact Info

Product

Resources

About