title: Behavioral and neural effects of intra-striatal infusion of anti-streptococcal antibodies in rats.
abstract: Group A β-hemolytic streptococcal (GAS) infection is associated with a spectrum of neuropsychiatric disorders. The leading hypothesis regarding this association proposes that a GAS infection induces the production of auto-antibodies, which cross-react with neuronal determinants in the brain through the process of molecular mimicry. We have recently shown that exposure of rats to GAS antigen leads to the production of anti-neuronal antibodies concomitant with the development of behavioral alterations. The present study tested the causal role of the antibodies by assessing the behavior of naïve rats following passive transfer of purified antibodies from GAS-exposed rats. Immunoglobulin G (IgG) purified from the sera of GAS-exposed rats was infused directly into the striatum of naïve rats over a 21-day period. Their behavior in the induced-grooming, marble burying, food manipulation and beam walking assays was compared to that of naïve rats infused with IgG purified from adjuvant-exposed rats as well as of naïve rats. The pattern of in vivo antibody deposition in rat brain was evaluated using immunofluorescence and colocalization. Infusion of IgG from GAS-exposed rats to naïve rats led to behavioral and motor alterations partially mimicking those seen in GAS-exposed rats. IgG from GAS-exposed rats reacted with D1 and D2 dopamine receptors and 5HT-2A and 5HT-2C serotonin receptors in vitro. In vivo, IgG deposits in the striatum of infused rats colocalized with specific brain proteins such as dopamine receptors, the serotonin transporter and other neuronal proteins. Our results demonstrate the potential pathogenic role of autoantibodies produced following exposure to GAS in the induction of behavioral and motor alterations, and support a causal role for autoantibodies in GAS-related neuropsychiatric disorders.
authors.affiliation: School of Psychological Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Dafna
authors.initials: D
authors.lastname: Lotan
authors.affiliation: Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Itai
authors.initials: I
authors.lastname: Benhar
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Kathy
authors.initials: K
authors.lastname: Alvarez
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Adita
authors.initials: A
authors.lastname: Mascaro-Blanco
authors.affiliation: School of Psychological Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel; The Feinstein Institute for Medical Research, Center for Autoimmune and Musculoskeletal Diseases, Manhasset, NY, USA.
authors.forename: Lior
authors.initials: L
authors.lastname: Brimberg
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Frenkel
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Madeleine W
authors.initials: MW
authors.lastname: Cunningham
authors.affiliation: School of Psychological Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel. Electronic address: djoel@post.tau.ac.il.
authors.forename: Daphna
authors.initials: D
authors.lastname: Joel
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D009043:Motor Activity; D051381:Rats; D011917:Rats, Inbred Lew; D011954:Receptors, Dopamine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin
keywords: Animal model; Dopamine; Pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS); Serotonin; Streptococcus group A (GAS); Sydenham’s chorea (SC)