Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer’s disease in wild-type, C57BL/6 mice
Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with cognitive decline and complete loss of basic functions. The ubiquitous apicomplexan parasite Toxoplasma gondii (T. gondii) infects up to one third of the world’s population and is implicated in AD...
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | http://link.springer.com/article/10.1186/s12974-018-1086-8 |
| _version_ | 1819172079659909120 |
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| author | Luisa Torres Sudie-Ann Robinson Do-Geun Kim Angela Yan Thomas A. Cleland Margaret S. Bynoe |
| author_facet | Luisa Torres Sudie-Ann Robinson Do-Geun Kim Angela Yan Thomas A. Cleland Margaret S. Bynoe |
| author_sort | Luisa Torres |
| collection | DOAJ |
| description | Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with cognitive decline and complete loss of basic functions. The ubiquitous apicomplexan parasite Toxoplasma gondii (T. gondii) infects up to one third of the world’s population and is implicated in AD. Methods We infected C57BL/6 wild-type male and female mice with 10 T. gondii ME49 cysts and assessed whether infection led to behavioral and anatomical effects using immunohistochemistry, immunofluorescence, Western blotting, cell culture assays, as well as an array of mouse behavior tests. Results We show that T. gondii infection induced two major hallmarks of AD in the brains of C57BL/6 male and female mice: beta-amyloid (Aβ) immunoreactivity and hyperphosphorylated Tau. Infected mice showed significant neuronal death, loss of N-methyl-d-aspartate receptor (NMDAR) expression, and loss of olfactory sensory neurons. T. gondii infection also caused anxiety-like behavior, altered recognition of social novelty, altered spatial memory, and reduced olfactory sensitivity. This last finding was exclusive to male mice, as infected females showed intact olfactory sensitivity. Conclusions These results demonstrate that T. gondii can induce advanced signs of AD in wild-type mice and that it may induce AD in some individuals with underlying health problems. |
| first_indexed | 2024-12-22T20:01:29Z |
| format | Article |
| id | doaj.art-6e2823bf1d9d4f1580b937bb95983a64 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-22T20:01:29Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-6e2823bf1d9d4f1580b937bb95983a642022-12-21T18:14:16ZengBMCJournal of Neuroinflammation1742-20942018-02-0115111910.1186/s12974-018-1086-8Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer’s disease in wild-type, C57BL/6 miceLuisa Torres0Sudie-Ann Robinson1Do-Geun Kim2Angela Yan3Thomas A. Cleland4Margaret S. Bynoe5Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell UniversityDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell UniversityDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell UniversityDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell UniversityDepartment of Psychology, Cornell UniversityDepartment of Microbiology and Immunology, College of Veterinary Medicine, Cornell UniversityAbstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with cognitive decline and complete loss of basic functions. The ubiquitous apicomplexan parasite Toxoplasma gondii (T. gondii) infects up to one third of the world’s population and is implicated in AD. Methods We infected C57BL/6 wild-type male and female mice with 10 T. gondii ME49 cysts and assessed whether infection led to behavioral and anatomical effects using immunohistochemistry, immunofluorescence, Western blotting, cell culture assays, as well as an array of mouse behavior tests. Results We show that T. gondii infection induced two major hallmarks of AD in the brains of C57BL/6 male and female mice: beta-amyloid (Aβ) immunoreactivity and hyperphosphorylated Tau. Infected mice showed significant neuronal death, loss of N-methyl-d-aspartate receptor (NMDAR) expression, and loss of olfactory sensory neurons. T. gondii infection also caused anxiety-like behavior, altered recognition of social novelty, altered spatial memory, and reduced olfactory sensitivity. This last finding was exclusive to male mice, as infected females showed intact olfactory sensitivity. Conclusions These results demonstrate that T. gondii can induce advanced signs of AD in wild-type mice and that it may induce AD in some individuals with underlying health problems.http://link.springer.com/article/10.1186/s12974-018-1086-8Alzheimer’s diseaseToxoplasma gondiiNMDARAmyloid betaOlfactory sensory neurons |
| spellingShingle | Luisa Torres Sudie-Ann Robinson Do-Geun Kim Angela Yan Thomas A. Cleland Margaret S. Bynoe Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer’s disease in wild-type, C57BL/6 mice Journal of Neuroinflammation Alzheimer’s disease Toxoplasma gondii NMDAR Amyloid beta Olfactory sensory neurons |
| title | Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer’s disease in wild-type, C57BL/6 mice |
| title_full | Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer’s disease in wild-type, C57BL/6 mice |
| title_fullStr | Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer’s disease in wild-type, C57BL/6 mice |
| title_full_unstemmed | Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer’s disease in wild-type, C57BL/6 mice |
| title_short | Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer’s disease in wild-type, C57BL/6 mice |
| title_sort | toxoplasma gondii alters nmdar signaling and induces signs of alzheimer s disease in wild type c57bl 6 mice |
| topic | Alzheimer’s disease Toxoplasma gondii NMDAR Amyloid beta Olfactory sensory neurons |
| url | http://link.springer.com/article/10.1186/s12974-018-1086-8 |
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