title: Shared Immune and Repair Markers During Experimental Toxoplasma Chronic Brain Infection and Schizophrenia.
abstract: Chronic neurologic infection with Toxoplasma gondii is relatively common in humans and is one of the strongest known risk factors for schizophrenia. Nevertheless, the exact neuropathological mechanisms linking T gondii infection and schizophrenia remain unclear. Here we utilize a mouse model of chronic T gondii infection to identify protein biomarkers that are altered in serum and brain samples at 2 time points during chronic infection. Furthermore, we compare the identified biomarkers to those differing between "postmortem" brain samples from 35 schizophrenia patients and 33 healthy controls. Our findings suggest that T gondii infection causes substantial and widespread immune activation indicative of neural damage and reactive tissue repair in the animal model that partly overlaps with changes observed in the brains of schizophrenia patients. The overlapping changes include increases in C-reactive protein (CRP), interleukin-1 beta (IL-1β), interferon gamma (IFNγ), plasminogen activator inhibitor 1 (PAI-1), tissue inhibitor of metalloproteinases 1 (TIMP-1), and vascular cell adhesion molecule 1 (VCAM-1). Potential roles of these factors in the pathogenesis of schizophrenia and toxoplasmosis are discussed. Identifying a defined set of markers shared within the pathophysiological landscape of these diseases could be a key step towards understanding their specific contributions to pathogenesis.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK; Department of Neuroscience, Erasmus Medical Centre, Rotterdam, The Netherlands;
authors.forename: Jakub
authors.initials: J
authors.lastname: Tomasik
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI;
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Schultz
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK;
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kluge
authors.affiliation: Stanley Laboratory of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Yolken
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK; Department of Neuroscience, Erasmus Medical Centre, Rotterdam, The Netherlands;
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI; vcarruth@umich.edu.
authors.forename: Vern B
authors.initials: VB
authors.lastname: Carruthers
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000276:immunology* / Q000378:metabolism*; D002908:Chronic Disease; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D012559:Schizophrenia / Q000276:immunology* / Q000378:metabolism*; D014122:Toxoplasma / Q000472:pathogenicity*; D016781:Toxoplasmosis, Cerebral / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers
keywords: Toxoplasma gondii; animal model; biomarker