title: Behavioral, pharmacological, and immunological abnormalities after streptococcal exposure: a novel rat model of Sydenham chorea and related neuropsychiatric disorders.
abstract: Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulin-dependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders.
authors.affiliation: School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Brimberg
authors.forename: Itai
authors.initials: I
authors.lastname: Benhar
authors.forename: Adita
authors.initials: A
authors.lastname: Mascaro-Blanco
authors.forename: Kathy
authors.initials: K
authors.lastname: Alvarez
authors.forename: Dafna
authors.initials: D
authors.lastname: Lotan
authors.forename: Christine
authors.initials: C
authors.lastname: Winter
authors.forename: Julia
authors.initials: J
authors.lastname: Klein
authors.forename: Allon E
authors.initials: AE
authors.lastname: Moses
authors.forename: Finn E
authors.initials: FE
authors.lastname: Somnier
authors.forename: James F
authors.initials: JF
authors.lastname: Leckman
authors.forename: Susan E
authors.initials: SE
authors.lastname: Swedo
authors.forename: Madeleine W
authors.initials: MW
authors.lastname: Cunningham
authors.forename: Daphna
authors.initials: D
authors.lastname: Joel
mesh_terms: D000293:Adolescent; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D002819:Chorea / Q000276:immunology / Q000382:microbiology / Q000523:psychology*; D004195:Disease Models, Animal; D005260:Female; D006120:Grooming / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000276:immunology / Q000382:microbiology / Q000523:psychology*; D009043:Motor Activity / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013290:Streptococcal Infections / Q000188:drug therapy / Q000276:immunology / Q000523:psychology*; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000276:immunology
chemical_list: D001323:Autoantibodies