Effect Of Rac1 On Fear Memory Enhance And Alzheimer’s Disease Forgetting

Learning is the neural activity to acquire and encode the information,while memory is to consolidate and retrieva the information.learning and memory are not independent two part but penetrate and influence each other,which include three stages:encoding,consolidation and retrieval.Learning and memory has two opposite ways:remember and forgetting.Our experience and scientific research data show that stress can induce well and enduring memory which is people’s talent to acclimatization.But,traumatic stressful event induce the strong fear memory which is harmful to people’s psychology and physiolgy health,which is posttraumatic stress disorder(PTSD)The Ebbinghaus curve showed that the forgetting begin from the learning and fast then slow(Ebbinghaus 1885).While,people with Alzheimer’s disease(AD)suffer from forgetting.The clinical feature of AD is forggeting begin from recent memory to longtime memory.Many research had reported that the reasons of pathogensis and the precipitating factor,but the moleclar mechanism is still unclear.Racl(TheRas-related C3 botulinum toxin substrate 1)is one member of Rho family and found in 1989,which regulate stress responsee origin from out membrane but also has neclear function.Rac1 is a small G protein,molecula swicher between two conformational states:one bound to GRP(active state),the other bound to GDP(inactive state).There are reported that Racl is involved in cognitive function,synaptic transmission and plasticity by regulating the cytoskeleton through a series of signalling pathways.But it is unclear about the mechanism of Racl in fear memory well and in AD.we uesed the contextual fear memory model to examine effect of the Rac1 on fear memory.We found that bothe stress and exogenous corticosterone(CORT)induced the down-regulation of Racl-GTP.Changes in the serum CORT level were negatively correlated with the level of Racl-GTP.Additionally,the antagonist of glucocorticoid receptors RU38486(RU)not only upregulated the expression of Racl-GTP but also impaired fear memory retrieval.Furthermore,the systemic administration of NSC23766(NSC),an inhibitor of Racl-GTP,improved the 1.5-and 24-h fear memory.Therefore,Racl plays a critical role in fear memory and may be a potential target in stress-related disorders.Then we explored the mechanism of Racl in the forgetting of AD.Firstly,we detected the spacial learning and memory of APP/PS1 from 2 to 8 months by Morris wate maze,the data showed that there are no significant difference between the 2 months compared with age-matched wild type mice,but the learning and memory of 4-7 months AD were impaired significantly compared with the age-mathed wild type mice.And the 72 h memory retrival of 3 months APP/PS1 treament by NSC(inhibitor of Racl activity)group was better than the vehicle group of APP/PS1 mice.The results showed the increasing of Rac1 activity(begin with 2 months old)was earlier than the AD biomarker and clinical feature(begin with 6-7 months).Furthmore,we found that Racl-GTP was co-localized with the astrocytes and PV neurons,which indicated that Racl-GTP involved the complex cellular function net.How the Racl-GTP work with the other neurons and mollecular is needed to further research.Our research indicated that Racl is an important melecular in fear memory enhancement and AD forgeeting.Theincreasing of Racl activity is earlier than the clinical feature and biomarker in AD model.So,Racl is a potential target for the PTSD and AD and is helpful to prevention,diagonosis and even recognitive disease recovery.