Age and Sex Related Behavioral Changes in Mice Congenitally Infected with Toxoplasma gondii: Role of dopamine and other neurotransmitters in the genesis of behavioral changes due to congenital infection and attempted amelioration with interferon gamma

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dc.contributor.authorGoodwin, David G.en
dc.contributor.committeechairLindsay, David S.en
dc.contributor.committeememberZajac, Anne M.en
dc.contributor.committeememberHrubec, Terry C.en
dc.contributor.committeememberKlein, Bradley G.en
dc.contributor.committeememberStrobl, Jeannine S.en
dc.contributor.departmentVeterinary Medical Sciencesen
dc.date.accessioned2014-03-14T20:14:20Zen
dc.date.adate2011-09-12en
dc.date.available2014-03-14T20:14:20Zen
dc.date.issued2011-07-12en
dc.date.rdate2011-09-12en
dc.date.sdate2011-07-26en
dc.description.abstractEvidence suggests that the neurotropic parasite Toxoplasma gondii may play a role in the development of cognitive impairments. My hypothesis was that congenital exposure to T. gondii would lead to detectable age and sex related differences in behavior and neurotransmitter levels in mice. The neurotransmitter dopamine and commonly used anti-schizophrenic agents were evaluated against T. gondii in human fibroblast cells. Dopamine caused a significant increase in tachyzoite numbers at 250 nM but not 100 nM and the drugs valproic acid, fluphenazine, thioridazine and trifluoperazine inhibited T. gondii development. The effects T. gondii infection had on behavior were examined using a congenital mouse model. Previous work demonstrated maternal immune stimulation (MIS) with interferon gamma (INF-g) resulted in decreased fetal mortality from congenital T. gondii infections; therefore I examined the effects of INF- g treatment of mothers to determine if protection from the behavioral effects of T. gondii occurred in their offspring. No differences in concentrations of neurotransmitters in the brains of congenitally infected mice were observed. I found that mice infected with T. gondii developed adult onset behavior impairments with decreased rate of learning, increased activity and decreased memory, indicating cognitive impairment for male mice and not female mice. My findings support the evidence T. gondii is a factor in the development of cognitive impairments. My results for T. gondii exposed male mice are consistent with the convention that males have more cognitive impairments in the prodromal stage of schizophrenia. MIS with IFN-g had a minimal effect on behavior post sexual maturity but had a greater effect on pre sexual maturity female mice which exhibited difficulties with spatial memory, coordination and the ability to process stimuli. The results indicate the behavior alterations from IFN- g are transient. When MIS is given prior to congenital infection with T. gondii, we detected no behavior deficits in any group of mice, including male mice post sexual maturity. Based on the results of my study, I must reject the hypothesis that neurotransmitter levels are influenced by congenital toxoplasmosis and accept the hypothesis that congenital T. gondii infection caused cognitive impairments in male mice post sexual maturity.en
dc.description.degreePh. D.en
dc.identifier.otheretd-07262011-145307en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-07262011-145307/en
dc.identifier.urihttp://hdl.handle.net/10919/28412en
dc.publisherVirginia Techen
dc.relation.haspartGoodwin_DG_D_2011.pdfen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectToxoplasma gondiien
dc.subjectmaternal immune stimulationen
dc.subjectschizophreniaen
dc.subjectinterferon gammaen
dc.titleAge and Sex Related Behavioral Changes in Mice Congenitally Infected with Toxoplasma gondii: Role of dopamine and other neurotransmitters in the genesis of behavioral changes due to congenital infection and attempted amelioration with interferon gammaen
dc.typeDissertationen
thesis.degree.disciplineVeterinary Medical Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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