| Object: Alzheimer’s disease(AD)is an insidious and progressive neurodegenerative disease.Progressive cognitive decline and memory loss are the main clinical features of AD.The formation of senile plaques(SP)by β-amyloid(Aβ)(molecular weight about 4000)and the hyperphosphorylation of tau protein to form neurofibrillary Tangle(neuro fibrillary tangles,NFT)is the main pathological and microscopic features of AD.There are several hypotheses about the etiopathogenisis of AD,but there is not any hypothesis that can really explain the pathophysiology of AD.The study found that APP/PS1 double transgenic mice significantly decreased learning ability,while the memory and memory barriers and so on.Studies have shown that the early cognitive and learning disorders of AD are mainly due to synaptic dysfunction in some brain regions.Synaptic plasticity is the basis of memory and storage in the central nervous system.The Notch pathway is closely related to abrupt plasticity.Notch1 protein is a receptor protein in Notch signaling pathway.This transmembrane protein can regulate neuronal regeneration and synaptic plasticity in mouse,and is the necessary protein for spatial memory formation in mice.Studies have shown that a large number of degenerative and necrotic neurons in AD transgenic mice are mainly associated with endoplasmic reticulum stress(ERS),which is caused by the deposition of abnormal proteins in the endoplasmic reticulum The main site when AD appears ERS,neuronal dysfunction,increased expression of GRP78,protein synthesis related to learning and memory will decline.AD disease accelerated with the progress of stress.Previous studies have shown that lycopene can effectively reduce the symptoms of neurodegenerative diseases in the AD Model mice and the reduction of brain Aβ deposition,increased learning behavior memory and cognitive function,but the specific mechanism of action of lycopene on AD mice remains unclear.Therefore,in this study,we use APP/PS1 transgenic mice to investigate whether lycopene can improve the learning and memory function of APP/PS1 transgenic mice in association with Notch1 protein and ERS.Methods: Gene identification was carried out on the transgenic mice of the transfer APP/PS1,and 6 of the 7 months old APP/PS1 transgenic mice were randomly selected as the model group and the drug administration group.Six randomly selected normal wild-type 7-month-old C57 mice were selected as normal control group.The rats were subjected to the behavioral test,Morris Water Maze Test(MWM)to test the spatial learning and memory and cognitive function of mice in each group.Western blot and immunohistochemistry were used to detect the expression of Notch1 and GRP78 in prefrontal cortex of mice.Results:The results of behavioral water maze test showed that compared with mice in control group,the model group had longer latency,less number of platforms per unit time,less spatial learning and memory ability,and decreased cognitive ability(P<0.05).After giving lycopene,the incubation period was shortened,and the number of platforms crossing the platform per unit time was increased(P<0.05)and spatial learning ability and cognitive ability were significantly improved,But there wasno significant difference with the normal group of mice(P>0.05).The results of Western blot and immunohistochemistry showed that the expression of Notch1 and GRP78 protein in the prefrontal cortex of mice in model group was higher than that in normal mice(P<0.05).After lycopene administration,The levels of Notch1 and GRP78 in the cortical were significantly lower than those in the untreated group(P<0.05).But there was no significant difference with the normal group of mice(P>0.05).Conclusions:Lycopene may be related to downregulation of Notch1 protein in learning and memory ability of APP/PS1 transgenic mice.Lycopene improves the learning and memory abilities of APP/PS1 transgenic mice may be related to the downregulation of GRP78 protein. |
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