Sodium Ferulate Protects Aβ_1-42–induced Memory Impairment And Hippocampal Neuron Damage By Promoting Notch1/Hes Signaling Pathway In Rat

Objective Synaptic loss is the cardinal feature linking neuropathology to cognitive decline in Alzheimer’s disease(AD),however,the mechanism of synaptic damage remains incompletely understood,there is still a lack of effective treatments.Recent evidence suggests that Notch signaling is affected by AD,Our previous study have shown the protective effect of Sodium ferulate(SF)on Aβ–induced hippocampal cell apoptosis in vitro and in vivo.SF can inhibit the apoptosis of hippocampal neurons induced by Aβ1-42,which may be via Notch1 signaling regulation.Therefore,In this study,we observe the protective effect of SF against soluble Aβ-induced neurotoxicity and astrogliosis in Rat hippocampus,We also investigated the regulatory role of SF on Notch1,NICD and Hes1.Moreover,we determined whether Notch1 pathway inhibition abolished the neuroprotective role of SF against soluble Aβ1–42 oligomers by decreasing NICD and Hes1 expression.Methods Forty male SD rats were randomly divided into control group,Ab1-42 group,SF group,SF+DAPT(Notch1 signal pathway inhibitor)group.Rats were given SF(100 mg×㎏-1 daily,ig)for 3 weeks prior to intracerebroventricular injection of Ab1-42(5μL,2mmol·L-1).DAPT was used to inject the abdominal of rat as100 mg·kg-1 for seven consecutive days.The contral group were intracerebroventricular injected with saline of the same volume.Two days later,Morris water maze was used to measure the learning and memory performance.Nissl staining and immunohistochemical technique for glial fibrillary acidic protein(GFAP)were used to determine the morphology of pyramidal neurons and astrocyte’s activation and infiltration in hippocmpal CA1 regions.The expression of several Notch1 signaling components,including Notch1,the Notch1 intracellular domain(NICD),Hairyand enhancer of split 1(Hes1,a downstream effector of Notch),were determined by Western blot method.Results Compared with the control group,Intracerebroventricular injection of A?1-42 in rats resulted in learning and memory impairments shown by longer escape latency and decreased percentage of time spent in the target quadrant(P<0.05).These behavioral dysfunctions were accompanied by astrocyte activation and infiltration,increased GFAP production(P<0.05),the expression of Notch1,NICD and Hes1 protein decreased significantly,(P<0.05).Compared with Aβ1-42 group,SF(100 mg?㎏-1 daily,ig)for 3 weeks markedly improved the learning and memory impairment(P<0.05),attenuated pyramidal neurons damage,the expression of GFAP protein decreased significantly(P<0.05),the expression of Notch1,NICD and Hes1 protein increased significantly(P<0.05),To investigate the mechanism of SF,the γ-secretase inhibitor DAPT was performed to block Notch signaling pathway,the results showed that the protective effect of SF was abolished by DAPT which effect by decrease the expression of NICD and Hes1 proteins(P<0.05).Conclusion The possible protective mechanism of SF on Aβ-induced hippocampal neuron damage via activation of Notch1/Hes signaling.