The Relationship Of 5-HT6R And Hippocampal Synaptic Plasticity In Licl-PILO Induced Chronic Temporal Lobe Epilepsy With Cognitive Impairment

?Purpose? In this study,using Morris water maze and Open-field test,to verify whether the chronic temporal lobe epilepsy(TLE)rats which ignited by lithium chloride-Pilocarpine(Li CI-PILO)accompanied with cognitive impairment.The vitro hippocampal field potential and Western blot reflect the change of hippocampal synaptic plasticity related indicators interfered by 5-HT6 R antagonist.Based on the electrophysiological and molecular biology,finding the potential mechanism in relationship of 5-HT6 R and chronic TLE.?Method? 1.Experimental animals were randomly divided into five groups: N=50,normal group(Vehicle),epilepsy model group 1(SE-2W),epilepsy model group 2(SE-4W),SB-271046 intervention group(SE+SB-271046)and Hp-?-CD group,n=10.2.The rats model of temporal lobe epilepsy were induced by lithium chloridepilocarpine.Only those rats achieve status epilepsy(SE,IV grade,at least 30 minuts,according to Racine classification)were included to further experiment.EEG also was exmainated.3.Morris water maze was used to observe the cognitive behavior of epileptic rats.4.The changes of hippocampal long-term potentiation(LTP)and the effect of 5-HT6 R antagonist SB-271046 on hippocampal LTP in chronic TLE rats were also observed in vitro.5.The expression of PSD-95 and NR2 B protein in hippocampus of TLE rats was detected by Western blot(WB).?Result?1.Ethological data: Morris water maze:the chronic phase(4W)of the TLE rats,there were obstacles of novel exploration(the number of wearing p(SE-4W 2.7 times vs Vehicle 5 times)<0.01).2.Vitro hippocampal field potential: the slope and amplitude of LTP in the temporal lobe epilepsy rats(2W),especially 4w/6w group,were lower than those in the control group(P <0.05).The slope respectively decreased 7%(p2W <0.005)and 19.9%(p4/6W <0.001),respectively.The amplitude was decreased 7%(p2W <0.005)and 19.9%(p 4/6W<0.001).3.Western blot: the relative ratio of grey value of PSD95 in SE-2Wgroup,SE-4W group,SE-6W group are under than the normal group(P <0.05),respectively,27.2%,40.2%,33.9%.The relative ratio of grey value of NR2 B as well as decreased than the normal(P <0.05),respectively,41.5%,54.8%,29.3%.By using SB-271046 can make PSD95/NR2 B slightly increased(P <0.05).?Conclusion? 1.The rat model of temporal lobe epilepsy induced by lithium chloride-pilocarpine put up cognitive impairment in the chronic phase.2.The related indicators of hippocampus synaptic plasticity declined in the chronic TLE: the slope and amplitude of LTP and the expression of PSD-95 and NR2 B were decreased.3.The 5-HT6 R antagonist SB-271046 can upregulate the above-mentioned indicators of hippocampus,with a certain extent,to improve the TLE rats cognitive impairment and emotional disorders.