A New T. gondii Mouse Model of Gene-Environment Interaction Relevant to Psychiatric Disease
Infection with the protozoan parasite, Toxoplasma gondii (T. gondii), was linked to several psychiatric disorders. The exact mechanisms of a hypothesized contribution of T. gondii infection are poorly understood, and it appears that only a subset of seropositive individuals go on to develop a mental...
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| Language: | English |
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Wiley
2018-01-01
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| Series: | Scientifica |
| Online Access: | http://dx.doi.org/10.1155/2018/7590958 |
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| author | Geetha Kannan Emese Prandovszky Emily Severance Robert H. Yolken Mikhail V. Pletnikov |
| author_facet | Geetha Kannan Emese Prandovszky Emily Severance Robert H. Yolken Mikhail V. Pletnikov |
| author_sort | Geetha Kannan |
| collection | DOAJ |
| description | Infection with the protozoan parasite, Toxoplasma gondii (T. gondii), was linked to several psychiatric disorders. The exact mechanisms of a hypothesized contribution of T. gondii infection are poorly understood, and it appears that only a subset of seropositive individuals go on to develop a mental illness, suggesting genetic vulnerability. In order to stimulate mechanistic studies of how exposure to T. gondii could interact with genetic predisposition to psychiatric disorders, we have generated and characterized a mouse model of chronic T. gondii infection in BALB/c mice with inducible forebrain neuronal expression of a C-terminus truncated dominant-negative form of disrupted-in-schizophrenia 1 (DN-DISC1). In this gene-environment interaction (GxE) model, exposing control and DN-DISC1 male and female mice to T. gondii produced sex-dependent abnormalities in locomotor activity and prepulse inhibition of the acoustic startle. No genotype- or sex-dependent effects were found on levels of anti-Toxoplasma IgG antibodies or anti-NMDAR or C1q antibodies. Our work demonstrates that a psychiatric genetic risk factor, DN-DISC1, modulates the neurobehavioral effects of chronic T. gondii infection in a sex-dependent manner. The present T. gondii model of GxE provides a valuable experimental system for future mechanistic studies and evaluation of new treatments. |
| format | Article |
| id | doaj-art-acead8d955ba48c7aebabead5eaf4f49 |
| institution | OA Journals |
| issn | 2090-908X |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Scientifica |
| spelling | doaj-art-acead8d955ba48c7aebabead5eaf4f492025-08-20T02:20:23ZengWileyScientifica2090-908X2018-01-01201810.1155/2018/75909587590958A New T. gondii Mouse Model of Gene-Environment Interaction Relevant to Psychiatric DiseaseGeetha Kannan0Emese Prandovszky1Emily Severance2Robert H. Yolken3Mikhail V. Pletnikov4Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USAStanley Neurovirology Laboratory, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USAStanley Neurovirology Laboratory, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USAStanley Neurovirology Laboratory, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USAInfection with the protozoan parasite, Toxoplasma gondii (T. gondii), was linked to several psychiatric disorders. The exact mechanisms of a hypothesized contribution of T. gondii infection are poorly understood, and it appears that only a subset of seropositive individuals go on to develop a mental illness, suggesting genetic vulnerability. In order to stimulate mechanistic studies of how exposure to T. gondii could interact with genetic predisposition to psychiatric disorders, we have generated and characterized a mouse model of chronic T. gondii infection in BALB/c mice with inducible forebrain neuronal expression of a C-terminus truncated dominant-negative form of disrupted-in-schizophrenia 1 (DN-DISC1). In this gene-environment interaction (GxE) model, exposing control and DN-DISC1 male and female mice to T. gondii produced sex-dependent abnormalities in locomotor activity and prepulse inhibition of the acoustic startle. No genotype- or sex-dependent effects were found on levels of anti-Toxoplasma IgG antibodies or anti-NMDAR or C1q antibodies. Our work demonstrates that a psychiatric genetic risk factor, DN-DISC1, modulates the neurobehavioral effects of chronic T. gondii infection in a sex-dependent manner. The present T. gondii model of GxE provides a valuable experimental system for future mechanistic studies and evaluation of new treatments.http://dx.doi.org/10.1155/2018/7590958 |
| spellingShingle | Geetha Kannan Emese Prandovszky Emily Severance Robert H. Yolken Mikhail V. Pletnikov A New T. gondii Mouse Model of Gene-Environment Interaction Relevant to Psychiatric Disease Scientifica |
| title | A New T. gondii Mouse Model of Gene-Environment Interaction Relevant to Psychiatric Disease |
| title_full | A New T. gondii Mouse Model of Gene-Environment Interaction Relevant to Psychiatric Disease |
| title_fullStr | A New T. gondii Mouse Model of Gene-Environment Interaction Relevant to Psychiatric Disease |
| title_full_unstemmed | A New T. gondii Mouse Model of Gene-Environment Interaction Relevant to Psychiatric Disease |
| title_short | A New T. gondii Mouse Model of Gene-Environment Interaction Relevant to Psychiatric Disease |
| title_sort | new t gondii mouse model of gene environment interaction relevant to psychiatric disease |
| url | http://dx.doi.org/10.1155/2018/7590958 |
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