title: Anti-streptococcus IgM antibodies induce repetitive stereotyped movements: cell activation and co-localization with Fcα/μ receptors in the striatum and motor cortex.
abstract: Group A beta-hemolytic streptococcus (GABHS) infections are implicated in neuropsychiatric disorders associated with an increased expression of repetitive stereotyped movements. Anti-streptococcus IgG presumably cross-reacts with elements on basal ganglia cells, modifies their function, and triggers symptoms. IgM may play a unique role in precipitating behavioral disturbances since variations in cortico-striatal activity occur in temporal congruity with peak IgM titers during an orchestrated immune response. We discovered in Balb/c mice that single subcutaneous injections of mouse monoclonal IgM antibodies to streptococcus group A bacteria induce marked dose-dependent increases in repetitive stereotyped movements, including head bobbing, sniffing, and intense grooming. Effects were antibody- and antigen-specific: anti-streptococcus IgG stimulated ambulatory activity and vertical activity but not these stereotypies, while anti-KLH IgM reduced activity. We suggest that anti-streptococcus IgM and IgG play unique roles in provoking GABHS-related behavioral disturbances. Paralleling its stereotypy-inducing effects, anti-streptococcus IgM stimulated Fos-like immunoreactivity in regions linked to cortico-striatal projections involved in motor control, including subregions of the caudate, nucleus accumbens, and motor cortex. This is the first evidence that anti-streptococcus IgM antibodies induce in vivo functional changes in these structures. Moreover, there was a striking similarity in the distributions of anti-streptococcus IgM deposits and Fos-like immunoreactivity in these regions. Of further importance, Fcα/μ receptors, which bind IgM, were present- and co-localized with anti-streptococcus IgM in these structures. We suggest that anti-streptococcus IgM-induced alterations of cell activity reflect local actions of IgM that involve Fcα/μ receptors. These findings support the use of anti-streptococcus monoclonal antibody administration in Balb/c mice to model GABHS-related behavioral disturbances and identify underlying mechanisms.
authors.affiliation: Department of Psychiatry, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Danhui
authors.initials: D
authors.lastname: Zhang
authors.forename: Ankur
authors.initials: A
authors.lastname: Patel
authors.forename: Youhua
authors.initials: Y
authors.lastname: Zhu
authors.forename: Allan
authors.initials: A
authors.lastname: Siegel
authors.forename: Steven S
authors.initials: SS
authors.lastname: Zalcman
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D001479:Basal Ganglia / Q000187:drug effects / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D007074:Immunoglobulin G / Q000494:pharmacology; D007075:Immunoglobulin M / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009044:Motor Cortex / Q000187:drug effects / Q000276:immunology; D016760:Proto-Oncogene Proteins c-fos / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology; D013239:Stereotyped Behavior / Q000187:drug effects*; D019956:Stereotypic Movement Disorder / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D058846:Antibodies, Monoclonal, Murine-Derived; C526791:Fcalpha-mu protein, mouse; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016760:Proto-Oncogene Proteins c-fos; D011961:Receptors, Fc; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin