The Effect Of BChE On Synaptic Information Transmission By Regulating Glu-Gln Cycle In Hippocampal CA1 In Mice

The normal formation of memory is an important function to maintain human basic physiological activities.Most of the patients with neuropsychiatric diseases such as Alzheimer's disease and post-traumatic stress disorder will produce memory disorders to varying degrees.Memory is formed by the cooperation of different brain regions,and the transmission of electrical signals and information integration between complex synapses dominated by neurons.Hippocampus is a very important structure in the brain,which plays the important role of learning and memory.CA1 area is an important area in the hippocampus responsible for information reception and transmission,which is related to learning,memory and cognitive function.BCh E can hydrolyze choline,which was previously thought to be a functional alternative to ache and widely expressed in the brain.However,from the results of recent experimental studies we know that BCh E may play an independent role in the hydrolysis of ACh without the change of ACh E activity.However,there is still a lack of experimental evidence and mechanism for specific brain regions.ObjectiveThis study provides in vivo and cellular experimental evidence for the biological mechanism of memory and the biological function of BCh E,and provides important data for clinical intervention and drug development of neuropsychiatric diseases with memory impairment as the main symptom.MethodsIn this study,firstly,the expression of BCh E in hippocampal CA1 area was down regulated by tool virus,and then the changes of memory,dendritic spines and excitatory neurotransmitters in scene fear memory model were explored,so as to clarify the regulation of BCh E in hippocampal CA1 area on memory.In addition,immunofluorescence,Western blotting and ELISA were used to explore the possible biological mechanism in vivo and cell models.In addition,in the third part of this study,on the basis of astrocyte AD model,KP2 was used as the enzyme activity inhibitor of BCh E,and the effect of KP2 on Glu Gln cycle in AD pathology was explored by means of immunoblotting and ELISA.ResultsKnockdown of BCh E in hippocampal CA1 can enhance fear memory,which may be related to the increase of Glu Gln cycle,but not the activity of ACh hydrolysis.It has also been verified on the cell model.We also suggest that BCh E in hippocampal CA1 regulates the GluGln cycle and the enhancement of fear memory may depend on GS in astrocytes.This study provides a new mechanism to explain the regulatory role of BCh E in highlighting information transmission.