Effects Of Fluoxetine On Learning And Memory And A?protein In AD Mice

Background and Objective:Alzheimer disease is a kind of neurodegenerative diseases,which is often found in geriatric population.Clinically,it is often assumed that a distinct decline of cognitive function is a symptom of AD.Pathologically,AD is characterized by the accumulation of amyloid beta and the stacking of neurofibrillary tangles in cells.The accumulation of amyloid beta plays a significant role in the whole diseases process.In the meantime,Alzheimer disease will cause brain atrophy and hippocampal atrophy.Lack of effective methods and laboratory model,the process of diagnosis and cure goes slowly.Because of the increase of the elderly population and limited diagnostic tools,the high morbidity and disability of AD has been a serious problem in human health.The epidemiological studies show that millions of people suffer from Alzheimer disease and relating dementia.As Chinese population ages,the prevalence of AD rises.This situation has aroused high interest from national government,and brings heavy burden to individuals,families,and the society.However,there are still no effective treatments to prevent the progression of AD or to slow it down.If there is a strategy that can delay the progression of AD symptoms,slow down clinicopathological advance and improve prognostic,no matter how minimal the effect is,it will make a great contribution to relieve the stress of society development and the burden of families.Therefore,it is imperative to actively explore the pathogenesis of AD and discover treatments to improve patients conditions.According to statistics reports,50% of AD patients,especially patients in the advanced stage,often suffered depression.A variety of antidepressants have been applied in clinical treatment.Among of them,fluoxetine is more widely-used and safe.Researchers find that fluoxetine can significantly improve the cognitive function of patients and their daily living ability.Combined with fluoxetine,therapeutic drugs for AD work better than the single AD drug therapy.However,it is still not clear that if antidepressants(eg.The early intervention)have an effect on memory disorder and pathology.With the APP/PSI double transgenesis Alzheimer disease rats,this study intends to investigate that how early antidepressants affect the amyloid beta and learning and memory abilities,which has an active effect on expanding the clinical application of antidepressants,treatment of memory disorder caused by Alzheimer disease,andindividualized therapy.Method: Twenty healthy APP/PS1 mice aged 3 months were randomly divided into two groups:APP/PS1 model + saline group(NS),APP/PS1 model + fluoxetine(5mg/kg/d)group(FLX),In addition,wild type mice of the same age were selected as control group(WT).The behavior of mice in all groups was detected by Y-maze test and water maze test.the brain sections of 3-month-old and 6-month-old transgenic mice were stained with Congo red(Gongo Red)to detect A ? plaques in the brain.The protein levels of A ? 40 and A ? 42 were determined according to the instructions of ELISA kit(Colorimetric;Bio Source,Camarillo,CA).Result: 1.Expression of A ? plaques in APP/PS1 transgenic mice: a ? plaques were found in the brain of 3-month-old double transgenic mice,which was significantly lower than that of 6-month-old double transgenic mice.2.Animal behavior results:The results of Y-maze test showed that the times of correct response(21.74±2.92 vs 16.47±3.00,P<0.001)and active avoidance(6.35±1.24 vs 3.80±1.12,P<0.01)in fluoxetine group were significantly higher than those in NS group.The results of Morris water maze test showed that the times of crossing the original platform(4.11±0.89 vs 2.08±0.58,P<0.001)and the residence time of the original platform quadrant(25.66±0.69 vs 18.27±0.93,P<0.001)in fluoxetine group were significantly higher than those in NS group.The escape latency in fluoxetine group(19.22±0.51 vs 32.38±0.61,P<0.001)was significantly lower than that in NS group.3.The content of A ? protein in brain tissue of fluoxetine group was significantly lower than that of NS group(A?1-40:306.60±53.53 vs 366.29±25.38,P<0.001;A?1-42: 130.94±15.06 vs 180.77±37.11,P<0.001).Conclusion: Early fluoxetine intervention can significantly improve the learning and memory function of APP/PS1 transgenic dementia mice and reduce the content of A ? protein in the brain.