title: The effect of soybean isoflavone on the dysregulation of NMDA receptor signaling pathway induced by β-amyloid peptides 1-42 in rats.
abstract: 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.
authors.affiliation: School of Public Health, Capital Medical University, No. 10 Xitoutiao, You An Men Wai, Beijing, 100069, China.
authors.forename: Yuan-Di
authors.initials: YD
authors.lastname: Xi
authors.forename: Juan
authors.initials: J
authors.lastname: Ding
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.forename: Dan-Di
authors.initials: DD
authors.lastname: Zhang
authors.forename: Jin-Meng
authors.initials: JM
authors.lastname: Liu
authors.forename: Ling-Li
authors.initials: LL
authors.lastname: Feng
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013025:Glycine max / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D002147:Calmodulin; D017362:Cyclic AMP Response Element-Binding Protein; D007529:Isoflavones; D010446:Peptide Fragments; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C075222:amyloid beta-protein (1-42); D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2