Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation
151—Schizophrenia and Bipolar Disorder: Animal Models I
Sunday, November 10, 2013, 8:00 am - 12:00 noon
151.22: The effects of Toxoplasma gondii infection on behavior in Nurr1-null heterozygous mice
Location: Halls B-H
*J. B. EELLS1, A. VARELA-STOKES1, S. X. GUO-ROSS1, D. S. LINDSAY2; 1Mississippi St Univ., Mississippi State, MS; 2Dept. of Biomed. Sci. & Pathobiology, Virginia Tech., Blacksburg, VA
Abstract Body: Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that reproduces in cats but can infect most vertebrates by forming latent cysts primarily in brain and muscle tissue. In humans, approximately 30% of the population has been exposed to this parasite. Although latent infection in immuno-competent individuals was thought to be benign, more recent data has found associations between antibody titers to T. gondii with incidence of schizophrenia, severity of schizophrenia positive symptoms, slower reaction time, an increase in traffic accidents and some personality traits. The current study investigated the effect of T. gondii infection in Nurr1-null heterozygous (+/-) mice, a mouse model of susceptibility to altered behaviors that correlate with schizophrenia symptoms. Specifically, isolation of +/- mice after weaning disrupted sensory motor gating and elevated amphetamine stimulated dopamine release in the shell of the nucleus accumbens. Since the Nurr1 gene is necessary for the proper development and function of mesencephalic dopamine neurons and T. gondii can also affect dopamine neurotransmission, our hypothesis is that T. gondii will have a greater impact on dopamine related behaviors in Nurr1 +/- mice. To test this hypothesis, male and female wild-type (+/+) and +/- mice were injected subcutaneously with 1000 T. gondii tachyzoites. Mice were tested prior to infection and 8 weeks post infection for prepulse inhibition (PPI) and activity in an open field. Preliminary results found elevated open field activity in the +/- mice, as has been previously reported. Post-infection, there was a significant elevation in open field activity in the female +/- mice with no change in activity of the female +/+ mice. T. gondii infection resulted in a modest increase in activity in both the +/+ and +/- male mice. No differences in PPI were found due to the +/- genotype. Female mice had significantly reduced PPI compared to the male mice. T. gondii infection had no effect on PPI on the male mice, however, it elevated PPI in the +/+ female mice. These data suggest that T. gondii infection can alter behavior in a genotype specific manor in rodents. Due to the prevalence of T. gondii infection in humans and the potential to alter human behavior, it is important to understand the mechanism(s) through which T. gondii can alter brain function and the genes that may enhance the susceptibility to this effect.
Lay Language Summary: Our preliminary data suggest that, in a genetic mouse model of schizophrenia, behavioral alterations are more pronounced when infected with the parasite, Toxoplasma gondii. Mice with a genetic mutation that disrupts the function of one gene linked to schizophrenia had altered levels of anxiety and exploratory behavior, behaviors associated with mental illness, that were more pronounced in infected mice. T. gondii is a parasite that infects between 20-30% of the U.S. population. It reproduces in cats and is shed into the environment through cat feces. T. gondii can infect most warm blooded vertebrates. Humans are typically infected by eating undercooked meat or improperly washed vegetables, changing cat litter and performing activities that place them in contact with soil, such as gardening. Currently, these infections are considered benign; however, evidence is accumulating that suggests that infection with this parasite could possibly alter human behavior and, in some cases , contribute to or exacerbate mental illness. Evidence to support this includes an association between high levels of antibodies to this parasite, indicating exposure, and having a mental illness such as schizophrenia. Currently, schizophrenia is thought to be caused by a combination of certain genetic predispositions in combination with a developmental or environmental insult, the latter including exposure to a infectious agent. Clearly, infection with T. gondii does not itself cause mental illness. Our data, however, suggest that infection with T. gondii could affect behavior and possibly exacerbate mental illness in genetically susceptible individuals. To test our hypothesis, normal mice and mutant mice were infected with T. gondii and tested for behaviors that measure anxiety, exploratory activity and regulation of sensory control. The gene that was deleted is involved in the development of neurons that make the neurotransmitter dopamine. The behaviors were chosen as they have been linked to symptoms of schizophrenia. Furthermore, these behaviors are also indicators of the function of dopamine in the brain. Our preliminary data indicate a greater effect on behavior in the mutant mice as compared to normal mice 8 weeks after T. gondii infection. These changes were different depending on sex of the mice and included an increase in exploratory activity in the mutant male mice and a decrease in anxiety related behavior in mutant female mice. The results from this study suggest that the effects on brain function and behavior as a result of this specific mutation can be exacerbated by infection with T. gondii. This data supports the hypothesis that certain individuals could be at greater risk for T. gondii infection precipitating behavioral changes or possibly contributing to a mental illness, such as schizophrenia. Understanding how T. gondii effects brain function in combination with various genetic mutations would be helpful in further evaluating the mechanisms contributing to these behavioral changes. Schizophrenia affects approximately 1% of the population. The symptoms can be severe and require treatment that is expensive and normally required throughout life. Additionally, having schizophrenia increases the risk of suicide. Understanding factors that lead to schizophrenia and identifying susceptible individuals is critical for providing better care and treatment to alleviate the consequences of this potentially devastating illness.
Neuroscience 2013 (43rd annual meeting of the Society for Neuroscience)Exit