Abstract
Abstract Alzheimer’s disease (AD) is a severe neuroinflammatory disease. CD4+Foxp3+ regulatory T cells (Tregs) play a pivotal role in maintaining immune tolerance in various inflammatory diseases. In this study, we sought to determine whether bee venom PLA2 promotes cognitive function in and modulates the patho-immunological features of AD in 3xTg-AD mice. PLA2 treatment significantly enhanced the cognitive function of the 3xTg-AD mice and increased glucose metabolism, as assessed with 18F-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) positron emission tomography (PET). The levels of amyloid beta (Aβ) deposits in the hippocampus were dramatically decreased following PLA2 treatment. This neuro-protective effect of PLA2 was associated with microglial deactivation and a reduction in CD4+ T cell infiltration. Interestingly, the neuroprotective effects of PLA2 were abolished in Treg-depleted mice. Therefore, the present studies strongly suggest that the modulation of peripheral immune tolerance by Treg might contribute to the neuroprotective effect of PLA2 in the 3xTg AD mice.
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