Effects And Mechanisms Of 5-HT₆R Ligands On Hippocampal Neuronal Injury In Pilocarpine Induced Rat

?Purpose?In order to investigate the role and mechanism of 5-HT₆R ligands on the hippocampal neuronal injury.Acute epileptic SD rats were induced by Lithium Chloride-Pilocarpine?LiCl-PILO?and pretreated with 5-HT₆R antagonist SB271046 and agonist WAY181187.We observed the damage of hippocampal neurons of rats in the acute phase of seizure.Molecular method was used to evaluate the changes of autophagy and mTOR in rats'hippocampus.?Methods?1.Group of experimental animals:Adult male Sprague-Dawley rats?N=70?were randomly divided into ten groups including Control group,Control+10%DMSO group,SE30mins group,SE30mins+10%DMSO group,SE1D group,SE1D+10%DMSO group,SE3D group,SE3D+10DMSO group,SE7D group and SE7D+10%DMSO group.LiCl-PILO was used to induce status epilepsy?SE?.According to Racine grades,seizures of grade IV and above last at least 30 minutes were recognized as succeed.2.Western Blot?WB?was used to determine the discrepancy of autophagy-related molecules?ATG7,Beclin1,and LC-3?between Control and each epileptic groups.3.Other experimental animals were grouped:Adult male Sprague-Dawley rats?N=40?were randomly divided into 4 groups:Control group,SE group,SE+SB271046 group and SE+WAY181187 group.SB271046 and WAY181187were pretreated before and during LiCl-PILO induced SE.4.The brains of rats were collected 3^rd days after SE and performed the following detection:Golgi staining was used to evaluate the survival neurons in hippocampus and total dendritic length,branch complexity,dendritic spine density of top dendrites of neurons in CA1.WB was used to detect the expression of ATG7,Beclin1,LC-3,mTOR and p-P70/P70.Electron microscopy was used to observe the morphological changes of neurons and weather there is autophagosome in them.?Result?1.The expression of ATG7,Beclin1 and LC-3II/I in hippocampus increased dynamically during the acute phase of SE,and reached the highest peak on the 3^rdd days.10%Dimethyl Sulfoxide?DMSO?had no effect on the above indicators as drug solvent in following study.2.The number of hippocampal neurons decreased.The total length,branch complexity and dendritic spine density of top dendrites of neurons in hippocampus CA1 were significantly decreased on the 3^rd days after SE.SB271046 relieved the above damage but WAY181187 has no effect on it.3.SB271046 decreased the expression of ATG7?Beclin1?LC-3II/I while increased p-P70/P70 in hippocampus.WAY181187 did not have effect on indicators'expression above.4.We observed shrinkage,aggregation,vacuolization in neurons located in hippocampal CA1 and autophagosomes appeared in them after SE.SB271046 can relieve the above morphological changes while WAY181187 had no effect on them.?Conclusion?1.Autophagy increases in rats`hippocampus in acute phase of seizure induced by LiCl-PILO.2.5-HT₆R antagonist SB271046 can alleviate the injury of hippocampal neurons in acute phase of SE induced by LiCl-PILO.3.The protection of SB271046 to neurons during acute phase of SE induced by LiCl-PILO may from reducing autophagy by activating of mTOR.