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

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with cognitive decline, resulting in a 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. 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. We previously reported 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. We have new data that suggests that T. gondii might be recruiting the NMDA receptor to the parasitophorous vacuole, a structure that protects T. gondii from the phagolysosomes of its host. This indicates that T. gondii might use the NMDA receptor of the host to survive and might explain the reduction of NMDAR that we observed with T. gondii infection. Since reduced NMDAR expression coincides with Aβ immunoreactivity, it is possible that T. gondii infection leads to reduced NMDAR expression which then leads to Aβ immunoreactivity.Support or Funding InformationThis work was supported by NIH grant R01 NS063011 to M.S BynoeThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.