Effects of diet and ovariectomy on <i>Toxoplasma gondii</i> brain infection: functional alterations and neuronal loss in rats

Epidemiological evidence associates <i>Toxoplasma gondii</i> latent infection with the development of neuropsychiatric disorders, and various immunological and environmental factors play key pathophysiological roles through host immune response alterations. We investigated the cognitive and motor alterations occurring in the terminal stage of <i>T. gondii</i> infection in rats, and whether a low-protein diet, a high-fat diet or ovariectomy may accelerate their development, given the role of malnutrition and menopause on immunity and resistance to infection. In two sets of experiments, 2-month-old (157.5 ± 4.3 g, <i>n</i> = 42) male (<i>n</i> = 18) and female (<i>n</i> = 24) Wistar rats were infected with <i>T. gondii</i> (ATCC 40050). Open-field and elevated plus maze tests were performed in the terminal stage of infection first and then in the early stage in low-protein diet-fed, high-fat diet-fed and ovariectomized infected rats. Late-stage (90 days) infected and early-stage (17 days) low-protein diet-fed groups showed significant decreases in body weight (42.42%↓, <i>P</i> = 0.016 and 57.14%↓, <i>P</i> < 0.001 versus non-infected, respectively), increases in body temperature (<i>P</i> = 0.001 and <i>P</i> < 0.001, respectively), decreases in blood glucose levels (<i>P</i> = 0.006 and <i>P</i> = 0.020, respectively), signs of cognitive and motor impairment and lower neuron counts. The alterations observed in high-fat diet-fed and ovariectomized infected animals were milder. Low-protein diet feeding to <i>T. gondii</i>-infected rats accelerated the occurrence of the infection terminal stage. Thus, a diet low in proteins could transform a slow early-stage <i>T. gondii</i> infection into an active neurotoxoplasmosis with neuropsychiatric manifestations and possible neurodegeneration in rats.