The Effect Of Orexin-1 Receptor On Cognitive Ability In Seizure Rats And Patients

Objective:This study aimed to investigate the effects of different doses of Orexin-1 receptor(OX1R)antagonist SB 334867 on the threshold of seizures and learning and memory function in mice with epilepsy induced by pentylenetetrazol(PTZ),and detecting the level of Orexin-A in brain tissue.To investigate the role of Orexin-1 receptor in the pathogenesis of epilepsy.Research objects and methods:Animal experiment:Male rats(weighing 25-30g)were randomly divided into 5 groups:1 control group(NS+NS):1 ml saline i.p,1ml saline i.v;2NS+PTZ group:1 ml saline i.p,PTZ i.v;3SB(3mg/kg)+ PTZ group:(3mg/kg)SB,PTZ i.v;4SB(10mg/kg)+ PTZ group:(10mg/kg)SB,PTZ i.v;5SB(30mg/kg)+ PTZ group:(30mg/kg)SB,PTZ i.v.Rats were injected intraperitoneally with SB 30 minutes before the test,and then the tail vein of the mouse was infused with a PTZ solution at a constant rate of 0.2 ml/min.Rats were observed during the infusion and the time between the start of the infusion and the beginning of the three convulsions was recorded in seconds.The learning and memory ability of each group of rats was tested by Morris water maze test.Brain Orexin-A levels were measured by enzyme-linked immunosorbent assay(ELISA).Clinical trial:20 patients with seizures(general seizures)within 24 hours were selected as epilepsy group,and 20 healthy subjects were selected as normal control group.Clinical data were collected:age,sex,body mass index,compared with normal control group.Statistical analysis was performed;and serum Orexin-A levels were measured by enzyme-limked immunosorbent assay(ELISA).Result:1.The 3,10,and 30 mg/kg doses of SB 334867 did not significantly affect the seizure threshold of mouse PTZ-induced myoclonus and systemic clonic.However,at doses of 10 and 30 mg/kg,SB 334867 significantly increased the onset threshold for tonic forelimb extension(P<0.05).2.Positioning navigation experiment:As the training time prolonged,the escape latency of each group of mice was correspondingly shortened.Compared with the NS+NS group,the average latency of the mice in each group was significantly prolonged(p<0.05).Compared with NS+PTZ,the 3 mg/kg dose of SB 334867 did not significantly affect the escape latency of mice,10,30 mg/kg.The escape latency of the SB 334867 epilepsy mice was significantly prolonged(p<0.05).3.Space exploration experiment:Compared with the NS+NS group,the number of times the mouse crossed the platform quadrant and the swimming time in the platform quadrant decreased in the NS+PTZ group.Compared with the NS+PTZ group,SB 334867 at doses of 3,10,and 30 mg/kg significantly reduced the number of crossings of the platform quadrant(p<0.05);SB 334867 at doses of 10 and 30 mg/kg significantly shortened swimming time in the platform quadrant of mice.(p<0.05).4.After PTZ induced tonic seizures,the total brain concentration of orexin A was reduced.Conclusions:1.Orexin-1 receptor antagonist SB 334867 can increase the seizure threshold in mice with acute epilepsy.2.The learning and memory ability of mice with epilepsy induced by pentylenetetrazol(PTZ)decreased.Orexin-1 receptor antagonist SB 334867 can further impair the learning and memory ability of epileptic mice.3.After PTZ induced tonic seizures,the total brain concentration of orexin-A was reduced.