title: Chronic Toxoplasma gondii in Nurr1-null heterozygous mice exacerbates elevated open field activity.
abstract: Latent infection with Toxoplasma gondii is common in humans (approximately 30% of the global population) and is a significant risk factor for schizophrenia. Since prevalence of T. gondii infection is far greater than prevalence of schizophrenia (0.5-1%), genetic risk factors are likely also necessary to contribute to schizophrenia. To test this concept in an animal model, Nurr1-null heterozygous (+/-) mice and wild-type (+/+) mice were evaluate using an emergence test, activity in an open field and with a novel object, response to bobcat urine and prepulse inhibition of the acoustic startle response (PPI) prior to and 6 weeks after infection with T. gondii. In the emergence test, T. gondii infection significantly decreased the amount of time spent in the cylinder. Toxoplasma gondii infection significantly elevated open field activity in both +/+ and +/- mice but this increase was significantly exacerbated in +/- mice. T. gondii infection reduced PPI in male +/- mice but this was not statistically significant. Aversion to bobcat urine was abolished by T. gondii infection in +/+ mice. In female +/- mice, aversion to bobcat urine remained after T. gondii infection while the male +/- mice showed no aversion to bobcat urine. Antibody titers of infected mice were a critical variable associated with changes in open field activity, such that an inverted U shaped relationship existed between antibody titers and the percent change in open field activity with a significant increase in activity at low and medium antibody titers but no effect at high antibody titers. These data demonstrate that the Nurr1 +/- genotype predisposes mice to T. gondii-induced alterations in behaviors that involve dopamine neurotransmission and are associated with symptoms of schizophrenia. We propose that these alterations in murine behavior were due to further exacerbation of the altered dopamine neurotransmission in Nurr1 +/- mice.
authors: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, United States of America.
authors: Jeffrey B
authors: JB
authors: Eells
authors: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, United States of America.
authors: Andrea
authors: A
authors: Varela-Stokes
authors: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, United States of America.
authors: Shirley X
authors: SX
authors: Guo-Ross
authors: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, United States of America.
authors: Evangel
authors: E
authors: Kummari
authors: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, United States of America.
authors: Holly M
authors: HM
authors: Smith
authors: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, United States of America.
authors: Arin D
authors: AD
authors: Cox
authors: Department of Biomedical Sciences & Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia, United States of America.
authors: David S
authors: DS
authors: Lindsay
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D001007:Anxiety / Q000235:genetics / Q000469:parasitology / Q000503:physiopathology / Q000523:psychology; D001362:Avoidance Learning; D001522:Behavior, Animal; D001835:Body Weight / Q000235:genetics; D002908:Chronic Disease / Q000523:psychology; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006579:Heterozygote; D008297:Male; D051379:Mice; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000172:deficiency* / Q000235:genetics*; D013216:Reflex, Startle / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics / Q000469:parasitology / Q000503:physiopathology; D055139:Sensory Gating / Q000235:genetics; D000069078:Seroconversion; D014122:Toxoplasma / Q000276:immunology / Q000502:physiology*; D014123:Toxoplasmosis / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology
chemical_list: D000953:Antigens, Protozoan; C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2