RESUMO
BACKGROUND: Toxoplasma gondii (T. gondii) is increasingly considered a risk factor for neurodegenerative diseases. However, there is only limited information on the development of drugs for T. gondii infection. Lentinan from Lentinula edodes is a bioactive ingredient with the potential to enhance anti-infective immunity. The present study aimed to investigate the neuroprotective effect of lentinan on T. gondii-associated cognitive deficits in mice. METHODS: A chronic T. gondii infection mouse model was established by administering 10 cysts of T. gondii by gavage. Lentinan was intraperitoneally administered 2 weeks before infection. Behavioral tests, RNA sequencing, immunofluorescence, transmission electron microscopy and Golgi-Cox staining were performed to assess the effect of lentinan on cognitive deficits and neuropathology in vivo. In vitro, the direct and indirect effects of lentinan on the proliferation of T. gondii tachyzoites were evaluated in the absence and presence of BV-2 cells, respectively. RESULTS: Lentinan prevented T. gondii-induced cognitive deficits and altered the transcriptome profile of genes related to neuroinflammation, microglial activation, synaptic function, neural development and cognitive behavior in the hippocampus of infected mice. Moreover, lentinan reduced the infection-induced accumulation of microglia and downregulated the mRNA expression of proinflammatory cytokines. In addition, the neurite and synaptic ultrastructural damage in the hippocampal CA1 region due to infection was ameliorated by lentinan administration. Lentinan decreased the cyst burden in the brains of infected mice, which was correlated with behavioral performance. In line with this finding, lentinan could significantly inhibit the proliferation of T. gondii tachyzoites in the microglial cell line BV2, although lentinan had no direct inhibitory effect on parasite growth. CONCLUSIONS: Lentinan prevents cognitive deficits via the improvement of neurite impairment and synaptic loss induced by T. gondii infection, which may be associated with decreased cyst burden in the brain. Overall, our findings indicate that lentinan can ameliorate T. gondii-related neurodegenerative diseases.