title: Striatal microinfusion of Tourette syndrome and PANDAS sera: failure to induce behavioral changes.
abstract: Rodent striatal microinfusions have been suggested as a model for assessing the behavioral effects induced by antineuronal antibodies. We used this approach to evaluate the proposed autoimmune etiology for Tourette syndrome (TS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Sera were assessed from patients with TS (n = 9) preselected based on the presence of elevated enzyme-linked immunosorbent assay optical densities against putamen homogenate and sera from patients with PANDAS (n = 8), selected from a larger group assayed for antibodies against a putamen synaptosomal preparation. The effect of antibodies against the streptococcal M5 protein were also studied. A total of 44 Fischer rats received bilateral infusion of sera: 23 ventral striatum (5 PANDAS, 5 TS, 5 anti-M5 protein, and 8 control); 21 ventrolateral striatum (5 PANDAS, 5 TS, 5 anti-M5 protein, and 6 controls). Cannulas were placed bilaterally and symmetrically by stereotactic techniques. After animals were allowed to recover for 1 week, sera were microinfused for 3 days. Animal behavior was then simultaneously quantified by daily observation and monitoring using automated activity boxes for 10 days after infusion. No significant alterations in stereotypic behavior or movement were observed between the PANDAS, TS, or anti-M5 protein and control groups. Our findings are in contrast to previous reports, and suggest the need for further investigations to determine the validity of the model and of autoimmune-mediated hypotheses for pediatric movement disorders.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Loiselle
authors.forename: Olivia
authors.initials: O
authors.lastname: Lee
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Moran
authors.forename: Harvey S
authors.initials: HS
authors.lastname: Singer
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood* / Q000276:immunology / Q000382:microbiology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001479:Basal Ganglia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D002352:Carrier Proteins / Q000276:immunology; D002648:Child; D046508:Culture Techniques; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D001523:Mental Disorders / Q000097:blood* / Q000276:immunology / Q000382:microbiology; D011699:Putamen / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013290:Streptococcal Infections / Q000097:blood* / Q000150:complications / Q000276:immunology; D005879:Tourette Syndrome / Q000097:blood* / Q000276:immunology / Q000382:microbiology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; C014689:streptococcal M protein