Fermented soybean foods (natto) ameliorate age-related cognitive decline by hippocampal TAAR1-mediated activation of the CaMKII/CREB/BDNF signaling pathway in senescence-accelerated mouse prone 8 (SAMP8).

Natto is a traditional fermented soybean-based food that has been an integral part of Japanese cuisine for several centuries. Although there have been extensive studies on the cognitive benefits of soybeans, only limited studies have examined the effects of natto on cognitive function. This study investigated the potential cognitive benefits of natto in senescence-accelerated mouse-prone 8 (SAMP8) mice. After 12 weeks of oral administering natto fermented for 18 h, the spatial learning and memory performance were improved compared with those in SAMP8 control mice. Furthermore, activation of the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element-binding protein (CREB) signaling and -methyl-D-aspartate receptor (NMDAR)-calcium/calmodulin-dependent protein kinase II (CaMKII) cascade was observed in the hippocampus of SAMP8 mice that were fed natto. Additionally, natto administration upregulated trace amine-associated receptor 1 (TAAR1) as a modulator of NMDAR. These findings suggest that natto ameliorates cognitive decline by activating the TAAR1-mediated CaMKII/CREB/BDNF signaling pathway in the hippocampus of SAMP8 mice.