Effect And Mechanism Of Sesamin On Cognitive Impairment In Female APP/PS1 Alzheimer's Disease Mice

With the development of nowadays society,the aging trend is gradually intensified,and the health problems of the elderly are attracting more and more attention.Neurodegenerative diseases,such as alzheimer's disease,which cause degeneration and death of nerve cells,are a major threat to health in old age.Women suffer from alzheimer's disease more often than men because of the lack of estrogen after menopause.In recent years,the use of natural food functional components to intervene neurodegenerative diseases has become a research hotspot in the field of food molecular nutrition.Sesamin is a lignin extracted from sesame.It belongs to phytoestrogens and has antidepressant and neuroprotective effects.This study provides a clue to understand the mechanism of sesamin as a phytoestrogen in alleviating cognitive impairment and suggests the possible beneficial stages of supplementing sesamin.The main research contents of this paper are as follows:(1)The effects of Sesamin on cognitive impairment in 6-month-old and 9-month-old female APP/PS1 mice were studied.In the experiment,sesamin(0.05%,w/w)was used to intervene the mice for 12 weeks,and the learning and memory ability and cognitive function of the experimental animals were evaluated by the behavioral detection method of new object recognition test.The experimental results showed that sesamin could improve the cognitive impairment of 12-month-old female APP/PS1 mice,but it did not improve the cognitive impairment of 9-month-old mice.(2)The effects of Sesamin on the aggregation of ? amyloid and neuroinflammation in the brain of APP/PS1 mice were studied by using 6-month-old and 9-month-old female APP/PS1 model mice.The results showed that sesamin significantly improved the aggregation of ?-amyloid,inhibited the over activation of glial cells and the expression of related inflammatory factors such as IL-1? and Iba-1,and significantly promoted the expression of postsynaptic density protein The expression of PSD-95 can enhance synaptic plasticity and improve nerve injury.In addition,sesamin can significantly reduce the expression of amyloid precursor protein(APP)in the brain of 12-month-old mice and increase the expression of recombinant human insulin degrading enzyme(IDE)in the brain of 9-month-old and 12-month-old mice,thus inhibiting the synthesis of ?-amyloid and the degradation of ?-amyloid.The results of Western blotting showed that sesamin supplementation could activate AKT-PI3 K signaling pathway in mouse brain.(3)In vitro experiments,SH-SY5 Y cells were treated with 20 ?M A?25-35 and 0,10,25,and 50 ?M concentration gradients of sesamin.The results show that sesamin significantly inhibits A?25-35-induced neurotoxicity in SH-SY5 Y cells.The inhibition of ER personal antagonist PHTPP was applied to explore the mechanism of the neuroprotective effect of sesamin by combining with ER personal.The SH-SY5 Y cells were treated with 20 ?M A?25-35,1 ?M ER? antagonist PHTPP and 25 ?M sesamin.It was found that sesamin increased the expression of PSD-95 and IDE through the ER?-AKT-PI3 K signaling pathway,thereby reducing A?25-35-induced neurotoxicity.In summary,sesamin can interfere with cognitive impairment in mice caused by Alzheimer's disease and ?-amyloid aggregation and neuroinflammation in the brain of mice.The effect of sesamin on alzheimer's disease and its potential mechanism were discussed.