{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T13:03:48Z","timestamp":1761311028260,"version":"3.41.0"},"reference-count":114,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2015,4,9]],"date-time":"2015-04-09T00:00:00Z","timestamp":1428537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Latent infection with<jats:italic>Toxoplasma gondii<\/jats:italic>is common in humans (approximately 30% of the global population) and is a significant risk factor for schizophrenia. Since prevalence of<jats:italic>T<\/jats:italic>.<jats:italic>gondii<\/jats:italic>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<jats:italic>T<\/jats:italic>.<jats:italic>gondii<\/jats:italic>. In the emergence test,<jats:italic>T<\/jats:italic>.<jats:italic>gondii<\/jats:italic>infection significantly decreased the amount of time spent in the cylinder.<jats:italic>Toxoplasma gondii<\/jats:italic>infection significantly elevated open field activity in both +\/+ and +\/- mice but this increase was significantly exacerbated in +\/- mice.<jats:italic>T<\/jats:italic>.<jats:italic>gondii<\/jats:italic>infection reduced PPI in male +\/- mice but this was not statistically significant. Aversion to bobcat urine was abolished by<jats:italic>T<\/jats:italic>.<jats:italic>gondii<\/jats:italic>infection in +\/+ mice. In female +\/- mice, aversion to bobcat urine remained after<jats:italic>T<\/jats:italic>.<jats:italic>gondii<\/jats:italic>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<jats:italic>T<\/jats:italic>.<jats:italic>gondii<\/jats:italic>-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.<\/jats:p>","DOI":"10.1371\/journal.pone.0119280","type":"journal-article","created":{"date-parts":[[2015,4,9]],"date-time":"2015-04-09T17:59:30Z","timestamp":1428602370000},"page":"e0119280","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Chronic Toxoplasma gondii in Nurr1-Null Heterozygous Mice Exacerbates Elevated Open Field Activity"],"prefix":"10.1371","volume":"10","author":[{"given":"Jeffrey B.","family":"Eells","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Varela-Stokes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirley X.","family":"Guo-Ross","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evangel","family":"Kummari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly M.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arin D.","family":"Cox","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Lindsay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2015,4,9]]},"reference":[{"key":"pone.0119280.ref001","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ajhg.2012.06.018","article-title":"Exome sequencing followed by large-scale genotyping suggests a limited role for moderately rare risk factors of strong effect in 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