Pediococcus acidilactici reduces tau pathology and ameliorates behavioral deficits in models of neurodegenerative disorders.

BACKGROUND: Alzheimer's disease (AD), affecting many elders worldwide, is characterized by A-beta and tau-related cognitive decline. Accumulating evidence suggests that brain iron accumulation is an important characteristic of AD. However, the function and mechanism of the iron-mediated gut-brain axis on AD is still unclear. METHODS: A Caenorhabditis elegans model with tau-overexpression and a high-Fe diet mouse model of cognitive impairment was used for probiotic function evaluation. With the use of qPCR, and immunoblotting, the probiotic regulated differential expression of AD markers and iron related transporting genes was determined. Colorimetric kits, IHC staining, and immunofluorescence have been performed to explore the probiotic mechanism on the development of gut-brain links and brain iron accumulation. RESULTS: In the present study, a high-Fe diet mouse model was used for evaluation in which cognitive impairment, higher A-beta, tau and phosphorylated (p)-tau expression, and dysfunctional phosphate distribution were observed. Considering the close crosstalk between intestine and brain, probiotics were then employed to delay the process of cognitive impairment in the HFe mouse model. Pediococcus acidilactici (PA), but not Bacillus subtilis (BN) administration in HFe-fed mice reduced brain iron accumulation, enhanced global alkaline phosphatase (AP) activity, accelerated dephosphorylation, lowered phosphate levels and increased brain urate production. In addition, because PA regulated cognitive behavior in HFe fed mice, we used the transgenic Caenorhabditis elegans with over-expressed human p-tau for model, and then PA fed worms became more active and longer lived than E.coli fed worms, as well as p-tau was down-regulated. These results suggest that brain iron accumulation influences AD risk proteins and various metabolites. Furthermore, PA was shown to reverse tau-induced pathogenesis via iron transporters and AP-urate interaction. CONCLUSIONS: PA administration studies demonstrate that PA is an important mediator of tau protein reduction, p-tau expression and neurodegenerative behavior both in Caenorhabditis elegans and iron-overload mice. Finally, our results provide candidates for AP modulation strategies as preventive tools for promoting brain health. Video Abstract.

"Support the strong" or "Help the weak?": The effects of social comparison and social distance on cooperative behavior in the dictator game.

Within an object-interdependent context, we conducted three experiments to investigate the influence of social comparisons on cooperative behavior, as well as to assess the mediating and moderating effects of related variables. In Experiment 1 (n = 207), we examined whether social comparisons impact cooperative behavior toward a comparator in a dictator game task. Here, we specifically focused on the mediating effects of evaluation of others' competence, along with three other potential mediators: self-competence evaluation, positive emotions, and negative emotions. Following the insights gained from Experiment 1, we proceeded to Experiments 2 (n = 279) and 3 (n = 298) to further explore whether social distance moderates the mediating effect of evaluation of others' competence. The results of all three experiments consistently indicated that upward (vs. non-) comparison facilitated cooperative behavior, whereas downward (vs. non-) comparison hindered it. Furthermore, our findings revealed that evaluation of others' competence served as a mediator between social comparison and cooperative behavior when the comparator (i.e., the cooperative partner) was perceived as being at a far-distance, whereas the mediating effect of evaluation of others' competence disappeared when social distance was close. These results reveal the pivotal role of evaluating others' competence and social distance in social interactions from the perspective of social comparison, which provides insights into how to promote cooperative behavior.