摘要Alzheimer's disease(AD)is a serious disease associated with cognitive impairment,and synaptic loss and amyloid-beta(Aβ)deposition are closely related to its pathogenesis.Docosahexaenoic acid(DHA)has been reported to alter the cognitive impairment associated with aging and reduce the risk of long-term development of AD.However,the effects of Aβ on synapses and whether DHA has a protective effect on synapses remain unclear.In this study,APPSwe/PSEN1dE9 transgenic and wild type mice were used as experimental subjects to explore the effect of DHA on synaptic structure and function damaged by Aβ.Results showed that a large amount of Aβ was deposited in the brain of AD mice,and DHA intervention decreased the Aβ deposition(P＜0.05).DHA decreased the apoptosis of nerve cells and the oxidative stress level induced by Aβ(P＜0.01).Transmission electron microscopy results showed that DHA improved the synaptic structure and number,and the expression of synaptophysin was significantly upregulated by DHA(P＜0.01).Besides,neurotransmitter release was regulated after DHA intervention,including the decreased Glu level and increased γ-aminobutyric acid level,as well as the activity of ATPase was also increased by DHA.Importantly,the phosphorylation levels of tyrosine kinase B(TrkB),phospholipase C-gamma-1,calcium/calmodulin-dependent protein kinase Ⅱ,extracellular regulated protein kinases(ERK1/2),and cAMP-response element binding protein(CREB)were upregulated by DHA(P＜0.01).These data indicated that DHA could improve synaptic structure and function through the TrkB-Erk1/2-CREB pathway,thus playing a positive role in the pathological process of AD.