Effect Of Z-octadec-9-ene-propane Sulfonamide On Learning And Memory Of Dementia Mice

Memory is one of the main functions in human brain and a high-level neurophysiological activity of the mammalian brain.However,the abilities of learning and memory would decrease gradually with age,and senile dementia would be result without intervening.Dementia is a common disease characterizing by cognitive dysfunction in the elderly.With the improvement of medical care and population aging,the increased number of dementia patients means a heavy burden to patients' families and society.Alzheimer's disease(AD),a central nervous system degenerative disease,seriously affect social and life skills,with clinical symptom of mainly progressive neurological disorders such as progressive memory impairment,cognitive dysfunction,personality changes and language disorders.Therefore,the early intervention of the drug to AD is one of the hot topics in medical ethics,which has positive social significance and plays an active role in promoting the social establishment.However,the etiology and pathogenesis of AD is still unclear.The cholinergic theory,which proposed more than 30 years ago,is still the research focus of drug therapy of AD.In recent years,the function of Oleoylethanolamide(OEA)in the brain gradually attracted people's attention.Previous studies in Xiamen University have shown that OEA has a neuroprotective effect on cerebral ischemia.However,OEA has no oral activity,because it would break down into oleic acid and ethanolamine in the intestine.Z-octadec-9-ene-propane sulfonamide(N15)is a structural modification product of OEA,which retains the original activity and has the antihydrolytic activity.Acetylcholine is most closed to learning and memory,existing as a neurotransmitter in vesicles of cholinergic neurons,and is rapidly hydrolyzed by cholinesterasein the intercellular space choline and acetic acid after released.So the acetylcholine content in cerebral cortex and hippocamp can determine the learning and memory ability of mice.Synaptic plasticity related protein is closed to neurotransmitter conduction and neurotrophic factor transmission,which has great significance for learning and memory research.Object:To determine the effect of Z-octadec-9-ene-propane sulfonamide(N15),an OEA structural analogues,on the improvement of learning and memory function in mice,and explore its treatment mechanism in alzheimer's disease.Methods:1.We use Morris water maze test the effect of N15 on learning and memory ability in scopolamine-induced dementia mice.2.After the water maze test,ACh,AChE and real-time PCR were performed to detect the expression of neurotrophin-3(NT-3),brain-derived neurotrophic factor(BDNF),synaptophysin(SYP),growth associated protein(GAP-43)gene expression levels in hippocampus.Results:1.Morris water maze test results show that N15 significantly improved scopolamine-induced learning and memory in mice.2.The results of ACh,AChE and real-time PCR in hippocampus showed that compared with the model group,the ACh level increased and the AChE activity decreased significantly in N15-treated group.In the real-time PCR experiment,the expression levels of NT-3,BDNF,SYP and GAP-43 in N15 administration group were significantly higher than those in model group.Conculsion:1.N15 significantly improve scopolamine-induced learning and memory in mice;2.N15 improve learning and memory mechanism may be related to improving cholinergic system function,promote the expression of neurotrophic factor and enhance synaptic plasticity.