The Neuropsychology Mechanisms Of Propofol Protects Against The Impairment Of Learning-memory Induced By Electroconvulsive Shock In Depressed Rats Via The Pathway Of The Hyperphosphorylation Of Protein Tau

Protein Tau is a very unequal phosphoric microtubule associatedprotein, which affect the transport of substances in the axons of the neurons,whose phosphorylation is one of the key methods to regulate neuronalfunction. The hyperphosphorylation of protein Tau can damage thelearning and memory of rats. The impairment of learning-memory inducedby electroconvulsive shock in depressed rats is relevant to the functionfailure of glutamic acid signal system. The rise of glutamate which inducedby electroconvulsive shock in depressed rats can lead to the impairment oflearning-memory through up-regulate the hyperphosphorylation of proteinTau? Is this process related to the excitotoxicty of glutamate? Can theexcitatory amino acids receptor antagonists and propofolwhich play a roleas GluR antagonist inhibit this process? What are the similarities anddifferences about the effects and the neuropsychology mechanisms ofpropofol, ginsenoside Rg-1and lithium protects against the impairment oflearning-memory induced by electroconvulsive shock in depressed rats?The series of problems above attracted strong interest of researchers.Therefore, we engaged in this research in order to explore the mechanismof this process. PART ⅠThe electroconvulsive shock of different electric quantity and ofdifferent treatment number up-regulated the content of glutamate inthe hippocampus of the depression model rats whose olfactory bulbswere removedObjective This study explore the effect of the electroconvulsive shockof different electric current and different duration up-regulated the contentof glutamate in the hippocampus of depressed rats. Methods Thedepression model rats whose olfactory bulbs were removed wereestablished. As the analysis of variance of factorial design set up twointervention factors which are the electric quantity factor(three levels:25mA,50mA,75mA) and the treatment number factor(three level:3timeselectroconvulsive shock,3times electroconvulsive shock,9timeselectroconvulsive shock). Seventy-two adult depression model rats whoseolfactory bulbs were removed were randomly divided into six experimentalgroups (n=6, in each group). The hippocampus was removed within24hours after the course of electroconvulsive shock finished. Results Theelectroconvulsive shock can significantly up-regulated the content ofglutamate. The changes were correlated with the electric quantity and thetreatment number of the electroconvulsive shock. And both influencespresent additive effect. Conclusions Our results indicate that theelectroconvulsive shock up-regulated the content of glutamate in thehippocampus of rats.PART ⅡMK-801or CNQX reduces electroconvulsive shock-inducedimpairment of learning-memory and hyperphosphorylation of tau inWYK rats with depression-like behaviors Objective This study explore the reversion of the excitatory aminoacid receptor antagonists against the impairment of learning-memory andthe hyperphosphorylation of Protein Tau induced by electroconvulsiveshock in depressed rats. Methods As the analysis of variance of factorialdesign set up two intervention factors which are the electroconvulsiveshock (two levels: no disposition; A course of electroconvulsive shock) andthe excitatory amino acid receptor antagonists (three levels: iv Saline; ivNMDA receptor antagonist MK-801; iv AMPA receptor antagonistDNQX). Fourty-eight adult WYK rats were randomly divided into sixexperimental groups (n=8, in each group). The Morris water maze teststarted within1day after the course of electroconvulsive shock finished inorder to evaluate learning-memory. The hippocampus was removed fromrats within1day after the morris water maze test finished. Detect of thecontent of glutamate in the hippocampus of rats by High PerformanceLiquid Chromatography. Detect of the content of Protein Tau whichincludes Tau5(total protein Tau), p-PHF1Ser396/404, p-AT8Ser199/202,p-12E8Ser262in the hippocampus of rats with the methods ofimmunohistochemistry staining (SP) and Western blotting test. ResultsThe electroconvulsive shock and the glutamate ionic receptor blockers caninduce the impairment of learning-memory in depressed rats, extending theevasive latency time and shorten the space exploration time. And bothinfluences present subtract effect. The electroconvulsive shock cansignificantly up-regulated the content of glutamate in the hippocampus ofdepressed rats which was not affected by the glutamate ionic receptorblockers. The electroconvulsive shock and the glutamate ionic receptorblockers do not affect the total protein Tau in the hippocampus of rats. Theelectroconvulsive shock can up-regulated the hyperphosphorylation ofprotein Tau in the hippocampus of depressed rats which is can be reduced by the glutamate ionic receptor blockers. And both influences presentsubtract effect. Conclusions Our results indicate that the electroconvulsiveshock up-regulated the content of glutamate in the hippocampus ofdepressed rats, which up-regulated the hyperphosphorylation of protein Tauwhich can induce the impairment of learning-memory in depressed rats.PART ⅢPropofol protects against the impairment of learning-memory andreduces the hyperphosphorylation of protein Tau induced byelectroconvulsive shock in the depression model rats whose olfactorybulbs were removedObjective This study explore the reversion of the propofol against theimpairment of learning-memory and the hyperphosphorylation of proteinTau induced by electroconvulsive shock in depressed rats. Methods As theanalysis of variance of factorial design set up two intervention factorswhich are the electroconvulsive shock (two levels: no disposition; A courseof electroconvulsive shock) and the propofol (two levels:5ml Saline wasinjected peritoneally;5ml propofol was injected peritoneally by dosage of100mg/kg). Thirty-two the adult depression model rats whose olfactorybulbs were removed were randomly divided into four experimental groups(n=8, in each group). The Morris water maze test started within1day afterthe course of electroconvulsive shock finished in order to evaluatelearning-memory. The hippocampus was removed from rats within1dayafter the Morris water maze test finished. Detect of the content of glutamatein the hippocampus of rats by High Performance Liquid Chromatography.Detect of the content of Protein Tau which includes Tau-5(Total proteinTau), p-PHF1Ser396/404, p-AT8Ser199/202, p-12E8Ser262, GSK-3β1H8and PP-2Ain the hippocampus of rats with the methods of Western blotting test.Results The electroconvulsive shock and the propofol can induce the impairment of learning-memory in depressed rats, extending the evasivelatency time and shortening the space exploration time. And bothinfluences present subtract effect. The electroconvulsive shock cansignificantly up-regulated the content of glutamate in the hippocampus ofdepressed rats which was reduces by the propofol. And both influencespresent subtract effect. The electroconvulsive shock and the propofol doesnot affect the total protein Tau and protein PP-2A in the hippocampus ofrats. The electroconvulsive shock can up-regulated thehyperphosphorylation of protein Tau and the expression of GSK-3β1H8inthe hippocampus of depressed rats which is can be reduced by the propofol.And both influences present subtract effect. Conclusions Our resultsindicate that the electroconvulsive shock up-regulated the content ofglutamate in the hippocampus of depressed rats, which up-regulated thehyperphosphorylation of protein Tau through up-regulating the expressionof GSK-3β1H8, which can induce the impairment of learning-memory indepressed rats; and the propofol protects against the impairment oflearning-memory and reduce the hyperphosphorylation of protein Tauinduced by electroconvulsive shock in depressed rats through reducing theexpression of GSK-3β1H8and the content of glutamate in the hippocampus.PART ⅣComparison of the neuropsychology mechanisms of propofol andNMDA receptor antagonist protects against the impairment oflearning-memory induced by electroconvulsive shock in depressed ratsObjective This study explore the reversion of propofol and NMDAreceptor antagonist against the impairment of learning-memory and thehyperphosphorylation of protein Tau induced by electroconvulsive shock indepressed rats. Methods As the analysis of variance of factorial design setup two intervention factors which are the electroconvulsive shock (two levels: no disposition; a course of electroconvulsive shock) and the drugs(three levels: ip Saline; ip propofol; ip MK-801). Forty-eight adultdepression model rats whose olfactory bulbs were removed were randomlydivided into six experimental groups (n=8, in each group). The Morriswater maze test started within1day after the course of electroconvulsiveshock finished in order to evaluate learning-memory. The hippocampuswas removed from rats within1day after the Morris water maze testfinished. Detect of the content of glutamate in the hippocampus of rats byHigh Performance Liquid Chromatography. Detect of the expression ofprotein Tau which includes p-AT8Ser202and GSK-3β1H8in the hippocampusof rats with the methods of immunohistochemistry staining (SP) andWestern blotting test. Results The drugs (propofol and MK-801) and theelectroconvulsive shock can induce the impairment of learning-memory indepressed rats, extending the evasive latency time and shorten the spaceexploration time. And both influences present subtract effect. Theelectroconvulsive shock can significantly up-regulated the content ofglutamate, which was not affected by MK-801, in the hippocampus ofdepressed rats which was reduces by the propofol. And both influencespresent subtract effects. The electroconvulsive shock and the drugs do notaffect the total protein Tau in the hippocampus of rats. Theelectroconvulsive shock can up-regulated the hyperphosphorylation ofprotein Tau in the hippocampus of depressed rats which is can be reducedby propofol and MK-801. And the influences between theelectroconvulsive shock and the drugs present subtract effects. Our resultsindicate that the electroconvulsive shock up-regulated the content ofglutamate in the hippocampus of depressed rats, which up-regulated thehyperphosphorylation of protein Tau which can induce the impairment oflearning-memory in depressed rats; and propofol protects against the impairment of learning-memory and reduce the hyperphosphorylation ofprotein Tau induced by electroconvulsive shock in depressed rats. GSK-3βis the key protein in this signaling pathway. Conclusions Our resultsindicate that the electroconvulsive shock reduce the impairment oflearning-memory the hyperphosphorylation of protein Tau in depressed ratsthough up-regulated the content of glutamate.PART ⅤComparison of the neuropsychology mechanisms of propofol,ginsenoside Rg-1and lithium protects against the impairment oflearning-memory induced by electroconvulsive shock in depressed ratsObjective This study explore the reversion of propofol, ginsenosideRg-1, lithium against the impairment of learning-memory and thehyperphosphorylation of protein Tau induced by electroconvulsive shockand the concentration of glutamic acid in the hippocampus in depressed rats.Methods As the analysis of variance of factorial design set up twointervention factors which are the electroconvulsive shock groups (twolevels: no disposition; A course of electroconvulsive shock) and the drugintervention groups (four levels: Microinjection of propofol, ginsenosideRg-1and lithium,20μg1μl-1). Sixty-four adult depression model rats whoseolfactory bulbs were removed were randomly divided into eightexperimental groups (n=8, in each group). The Morris water maze teststarted within1day after the course of electroconvulsive shock finished inorder to evaluate learning-memory. Detect of the content of glutamate inthe hippocampus of rats by High Performance Liquid Chromatography.Detect of the content of protein Tau which includes Tau-5and p-AT8Ser202in the hippocampus of rats with the methods of Western blotting test.Results Propofol and the electroconvulsive shock can induce theimpairment of learning-memory in depressed rats. Ginsenoside Rg-1and lithium can protects against the impairment of learning-memory induced byelectroconvulsive shock in depressed rats. The electroconvulsive shock cansignificantly up-regulated the content of glutamate, which was reduces bypropofol. The electroconvulsive shock can up-regulated thehyperphosphorylation of protein Tau in the hippocampus of depressed ratswhich is can be reduced by these three medicines. Conclusions Our resultsindicate that propofol, ginsenoside Rg-1and lithium protects against theimpairment of learning-memory induced by electroconvulsive shock indepressed rats though reducing the hyperphosphorylation of protein Tau.The first two is not content with the glutamate in the hippocampus, withwhich lithium is not content.CONCLUSIONS OF THE TATOL PAPEROur results indicate that the electroconvulsive shock up-regulated thecontent of glutamate in the hippocampus of depressed rats, whichup-regulated the hyperphosphorylation of protein Tau throughup-regulating the expression of GSK-3β1H8, which can induce theimpairment of learning-memory in depressed rats. Propofol protects againstthe impairment of learning-memory and reduce the hyperphosphorylationof protein Tau induced by electroconvulsive shock in depressed ratsthrough reducing the expression of GSK-3β1H8and the content of glutamatein the hippocampus. GluR antagonists, ginsenoside Rg-1and lithiumprotects against the impairment of learning-memory induced byelectroconvulsive shock in depressed rats though reducing thehyperphosphorylation of protein Tau, too.