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Genistein (Gen), as a functional food in human diet, has shown many beneficial effects on neurodegenerative diseases such as Alzheimer's disease (AD). But the neuroprotective mechanism of Gen is not clear. Because synaptic failure is considered as the earliest phase in the pathogenesis of AD, we try to validate our hypothesis that synapse may be one target of Gen on protecting neurons. In this study, SH-SY5Y cells were pre-incubated with or without Gen for 2 h followed by the incubation with Aβ25-35 (25 μmol/L) for another 24 h. Flow cytometry, Western Blots, and RT-PCR analysis were used to test the synaptic factors. The data showed that Gen pre-treatment could reverse the Aβ25-35-induced down-regulation of synaptophysin and postsynaptic marker postsynaptic density-95. In addition, the down-regulation of NR1 and NR2B induced by Aβ25-35 which are subunits of N-methyl-D-aspartate receptor also could be antagonized by pre-treatment of Gen. Moreover, the factors of CaMKII/CREB signaling pathway were detected. The results showed that mRNA and protein expressions of (Ca(2+))/calmodulin(CaM), CaMKII/pCaMKII, and CREB/pCREB were significantly down-regulated by Aβ25-35, but they were all restored by the pre-treatment of Gen. Furthermore, Gen also maintained the intracellular Ca(2+) concentration which was disturbed by Aβ25-35. In conclusion, these results suggested that Gen could protect synaptic dysfunction induced by Aβ, and the mechanism might be associated with the regulation of synaptic markers and Ca(2+) level through activating CaM/CaMK/CREB signaling pathway.

Synaptic damage is the key factor of cognitive impairment. The purpose of this study was to understand the effect of soybean isoflavone (SIF) on synaptic damage induced by β-amyloid peptide 1-42 (Aβ1-42) in rats. Adult male Wistar rats were randomly divided into control, Aβ1-42, SIF, and SIF + Aβ1-42 (SIF pretreatment) groups according to body weight. SIF was treated orally by gavage in SIF and SIF + Aβ1-42 groups. After 14 days pretreatment with SIF or vehicle, Aβ1-42 was injected into the lateral cerebral ventricle of rats in Aβ1-42 and SIF + Aβ1-42 groups using miniosmotic pump. The level of Aβ1-42 and the expression of N-methyl-D-aspartic-acid receptor (NMDAR) were observed by immunohistochemistry. Reverse transcriptase polymerase chain reaction was used to detect the mRNA levels of NMDAR, calmodulin (CaM), calcium/CaM-dependent protein kinase II (CaMKII), cAMP-response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF). The results showed that Aβ1-42 down-regulated mRNA and protein expression of the NR1 and NR2B subunits of NMDAR, SIF pretreatment could reverse these changes. The mRNA expression of CaM, CaMKII, CREB, and BDNF were down-regulated by Aβ1-42, but they were all regulated by SIF pretreatment. These results suggest that SIF pretreatment could antagonize the neuron damage in rats induced by Aβ1-42, and its mechanism might be associated with the NMDA receptor and CaM/CaMKII/CREB/BDNF signaling pathway, which are the synaptic plasticity-related molecules.