Background: Toxoplasmagondii infects about one third of people around the world and is associated with neuropsychiatric disorders. But not everyone who has it ends up with behavioral symptoms, which is kind of interesting. The study aimed to investigate the two-hit hypothesis, basically testing if chronic stress makes the effects of the infection worse in mice, on behavior and cognition. Methods: Sixty Swiss Webster mice were included in the study divided into four groups (15 for each). Group 1 control, group 2 stressed animals exposed to the chronic unpredictable stress protocol, Group 3 infected with T. gondii, and group 4 received chronic unpredictable stress followed by T. gondii infection (infected-stressed). The stress was unpredictable and chronic, for four weeks. Behavioral tests included open field at week two, elevated plus maze at week four, novel object recognition at week six, and predator odor at week ten. At week twelve, mice were euthanised and examined for the brain cyst burden. Results: Double-hit mice performed novel object recognition test at levels of 0.06 ± 0.14, contrasted with 0.42 ± 0.09 in controls, indicating a strong impairment with a large effect size (p < .001, Cohen’s D = 3.27). Both infected groups lost their natural avoidance of predator odor, spending 31–34% of the test time in predator-associated zones versus 9.5% in controls (p < .001), and the effect of chronic stress did not significantly affect this. These functional impairments were strongly and dosedependently associated with the cyst burden, with correlation coefficients of −0.58 to −0.67 (all p < .001). Conclusion: Chronic stress and T. gondii infection have synergistic effects on anxietylike behaviors and cognitive impairments accompanied by increased parasite burden. This supports the two-hit hypothesis and potentially explaining heterogeneous psychiatric manifestations in human toxoplasmosis.
Nora El-Tantawy (Thu,) studied this question.