The Study On NAP Protecting Against Ketamine-induced Neurotoxicity In Young Rats

Objective: The main goals of this study are to determine whether NAP can reduce the phosphorylation levels of Tau ser404 and neuronal apoptosis in the rat hippocampus caused by ketamine,and protect the ability of learning and memory.And then we try to search for a new potential method to treat the neurotoxicity and the damages of learning and memory caused by ketamine.Methods:Eighty Sprague-Dawley rats of 7 days old were randomly divided into four groups,each group of 20,namely group NS,group NAP,group K and group N+K.Rats in group NS were intraperitoneally injected with normal saline,rats in group NAP were intraperitoneally injected with NAP,rats in group K were intraperitoneally injected with ketamine,rats in group N+K were intraperitoneally injected with NAP and ketamine.Each injection was diluted to 0.5ml.Injection was performed once a day for 3 consecutive days.NAP was injected half an hour before ketamine administration.24 hours after the last treatment,part of the rats were anesthetized,decapitated and the hippocampus were isolated for detection the Tau ser404 phosphorylation levels by Western blotting,part of the rats were anesthetized,decapitated and the hippocampi were isolated for detection of neuronal apoptosis by TUNEL.Finally,Morris water maze place navigation test and spatial probe test was adopted to explore the learning and memory function when the rats grown 27days old.Results:(?????????????)1?Compared with the rats in group NS,the ser404 phosphorylation levels of tau showed no significant difference in group NAP(P>0.05).Rats in group K and group N+K had higher Tau ser404 phosphorylation levels than rats in group NS(P<0.01).Compared with rats in group K,the tau phosphorylation level in group N+K was lower(P<0.01).2?TUNEL results shows,the apoptosis index at regions CA1 of rat s in group NS,group NAP,group K and group N+K are 11.8%±1.4%,11.7%±1.2%,59.8%±3.3% and 47.8±2%.There is no significant difference between rats in group NS and group NAP(P>0.05).The apoptosis inde x at regions CA1 of rats in group K and group N+K is higher than gro up NS(P<0.01).However,when compared with rats in group K,there is a lower apoptosis index at regions CA1 in group N+K(P<0.05).3?For the water maze test,there were no significant differences in the first three days(P>0.05).On day 4,the escape latency period of rats in each group continue to decrease,and there were no differences between rats in group NS,group NAP and group N+K(P>0.05).Furthermore,compared with the group NS,rats in group K took longer time to find the hidden platform on day 4(P<0.01).There were no significant differences with the escape latency of rats in group K and group N+K(P>0.05).Then on day 5,the escape latency between rats in group NS and group NAP have no significant differences(P>0.05),However,the escape latency of rats in group K were increased compared with group NS(P<0.01).When compared with rats in group K,the escape latency of group N+K were decreased(P<0.05).In the probe trial,the results showed that: compared with rats in group NS,the times of crossing the platform is less in group K(P<0.01)with no obvious difference between rats in group NAP and group N+K(P > 0.05).whereas the times of crossing the platform of rats in group N+K is higher than group K(P<0.05).the results of time in the target quadrant shows,there is no obvious difference between rats in group NS and group NAP(P>0.05).Rats in group K spent lower time in the target quadrant than rats in group NS(P<0.01).Rats in group N+K spent lower time in the target quadrant than rats in group NS(P<0.05).When compared with rats in group K,rats in group N+K spend significantly more time in the target quadrant(P<0.05).Conclusion: 1?Ketamine can lead to higher phosphorylation level of Tauand neuronal apoptosis in the rat hippocampus.Ketamine can also cause long-term spatial learning and memory ability damage after Ketamine anesthesia.2 ? NAP can reduce the neurotoxicity and learning and memory ability damage caused by ketamine,in which induction of tau phosphorylation and neuronal apoptosis in the hippocampus maybe one of the mechanisms.