Effects Of Propane-2-sulfonic Acid Octadec-9-enyl-amide On Learning And Memory Ability Aβ25-35-induced In Alzheimer’s Disease Model

Background:Alzheimer’s disease(AD)is a neurodegenerative disease that severely damages the quality of life.One of its main pathological features is the excessive deposition of Amyloid-beta(Aβ).Propane-2-sulfonic acid octadec-9-enylamide(N15)is a structural analogue of the endogenous active substance Oleoylethanolamine(OEA).Previous studies in our laboratory have confi rmed that N15 improves cognitive dysfunction after stroke by enhancing hippocampal neurogenesis,but the effect of N15 on AD is still unclear.Objective:To explore the improvement of cognitive function of AD by N15 and its related mechanism.Methods:Segment Aβ25-35 was injected into the lateral ventricle of the mouse to build the AD model.N15(50,100,and 200 mg/kg)was administered by gavage daily for 28 consecutive days,Morris water maze was used to test the learning and memory ability of mice in each group.The expression of neural factors and the morphology of neurons in the hippocampal CA1 region were detected.Congo red staining was used to detect the deposition of Aβ in the brain of each group and to detect the mRNA and protein expression levels of cutting amyloid precursor protein(alpha-secretase,reduce beta-secretase and gamma-secretase).Results:N15 promotes the production of brain-derived neurotrophic factor(BDNF)in AD model,improves the morphology of hippocampal neurons,plays a neuroprotective role,and improves cognitive dysfunction.Moreover,the neuroprotective effect of N15 on AD model is dose-dependent.N15 increases the expression of alpha-secretase,reduce beta-secretase and gamma-secretase expression,N15 may inhibit Amyloid precursor protein(APP)of amyloid production means,promote the un-amyloid production means,then reduce the generation of amyloid in the brain,and improve the condition of Aβ deposition in the brain,and the function is also dose-dependent.Conclusion:N15 improves cognitive dysfunction and decreases Aβ deposition in AD mice,possibly by regulating the expression of α-secretase,β-secretase and γsecretase.