Effects Of Selective 5-hydroxytryptamine 6 Receptor Agonist On Cognitive Function In Vascular Dementia Rats

Objective:To study the effects of selective 5-hydroxytryptamine 6（5-HT₆）receptor agonist on cognitive function in rats with vascular dementia（Va D）.The morphological changes of cells in CA1 area of rat hippocampus,Morris water maze to detect the escape latency,the times of crossing the platform and the changes of malondialdehyde（MDA）content and glutathione peroxidase（GSH-Px）activity in rat serum were observed to provide a theoretical basis for further exploring the ability of selective 5-HT₆R agonist to improve the impaired cognitive function in rats with vascular dementia.Methods:Healthy male SD rats（7 weeks old）,weighing 250±20g,acclimatization feeding for 1 week.The rats were randomly divided into model group,sham group,and selective 5-HT₆R agonist group,with 8 rats in each group.The model group and the selective 5-HT₆R agonist group were established by permanent bilateral common carotid artery occlusion to establish a vascular dementia model in rats,while the sham group only found bilateral common carotid arteries without occlusion.After 1week of surgery,rats in the model group and the selective 5-HT₆R agonist group were detection for behavioral tests,and those rats that did not meet the criteria for dementia were eliminated and the number of rats in each group that met the criteria for dementia was replenished with rats that met the criteria for dementia.The rats in the selective 5-HT₆R agonist group were given a selective 5-HT₆R agonist,EMD386088（5mg/kg）,intraperitoneally 1 time per day for 2 weeks.The rats in the model and sham groups were given an equal amount of saline intraperitoneally,and the rest of the steps were the same as those for the selective 5-HT₆R agonist group.At 4weeks after surgery,the rats in the three groups were subjected to HE staining to observe the cell morphology in the CA1 region of the hippocampus.The Morris water maze was used to test the escape latency and the number of crossing platform times in the rats of the three groups,Enzyme-linked Immunosorbent Assay（ELISA）was performed to determine the MDA content and GSH-Px activity in rat serum.Results:Compared with the sham group,the cell morphology of the hippocampal CA1 area in the model group was significantly damaged,the normal morphology of the cells was significantly changed,the nuclei appeared solidified and deeply stained,and the nucleoli in the cells were not clearly displayed.When the Morris water maze behavioral test was performed,the escape latency of rats was prolonged,and the difference in escape latency from day 2 was statistically significant（P<0.05）.The number of crossing platform times was reduced within 120s after removal of the platform,and there was a statistically significant change in the number of crossing platform times in both groups of rats（P<0.05）.the serum MDA content increased and GSH-Px activity decreased in the model group rats,and the changes of MDA and GSH-Px in the two groups were statistically significant（P<0.05）.Compared with the model group,the rats in the selective 5-HT₆R agonist group had better cell orphology in the damaged hippocampal region,behavioral tests of the Morris water maze suggested that the escape latency of the rats was shortened,and the difference in escape latency from day 3 was statistically significant（P<0.05）.The number of crossing platform times within 120s after removal of the platform increased and the change in the number of crossing platform times in both groups of rats was statistically significant（P<0.05）.the MDA content of the rats decreased and GSH-Px activity increased in the selective 5-HT₆R agonist group,and the changes in MDA content and GSH-Px activity in the serum of rats in both groups were statistically significant（P<0.05）.Conclusion:Selective 5-HT₆R agonist resulted in improved cell morphology in the damaged CA1 region of the rat hippocampus,enhanced impaired memory and learning ability in behavioral tests,reduced serum MDA levels,and increased GSH-Px activity indicating a reduction in the degree of oxidative stress in vascular dementia rats,suggesting that selective 5-HT₆R agonist improve cognitive function in vascular dementia rats.