Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer's disease in wild-type, C57BL/6 mice

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 (A beta) 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.