The Cognitive Function Change And JNK Expression In Hippocampus Of The PTZ Induced Female Epileptic Model’s Offspring

Objective:Epilepsy is a kind of nervous system common brain dysfunction syndrome, performance for the brain neurons supersynchronous discharge caused by the sudden, repeatability, transient nervous system disorders, have repeated attacks of clinical features. Our country’s existing epilepsy patients about6.5to9.1million, of which30%-40%of the people with epilepsy are prone to cognitive function obstacle, main show is inattention, study memory disorders, etc. The harm in addition to seizures itself, the cognitive impairment caused by epilepsy, also taken more and more attention by people, and has become a modern and hot spot in the study. Some of the people with epilepsy are women of reproductive age, accounts for about1/200of the total gestational age women each year, about0.3%to0.4%of the newborn from epilepsy mother for each year. Studies had shown epileptic seizures during pregnancy had influence on the offspring:the fetus low weight, small head, newborns and perinatal death, precocious, deformity and developmental delay. A lot of research had been done on the cognitive effects of the offspring whose mother had epilepsy and had epileptic seizures during pregnancy, however, it has been more on the antiepileptic drugs, and the influence of epilepsy itself is less been reported. Based on that, we create a PTZ induced female epilepsy model to learn the single repeated seizures’ influence during pregnancy on the cognition of the offspring and the protein expression in hippocampus of JNK and p-JNK.Methods:We establish female epileptic model inducing by pentylenetetrazol (PTZ) intraperitoneal injection. Adult male SD rats (7to8weeks, weight200±20g) were selected through Y-Maze tests and randomized into3groups, the normal control (NC) group, saline control (SC) group, and the PTZ group,for each group n=10.PTZ group:every morning9:00-10:00, the model rats were given PTZ35mg per kilogram intraperitoneally, after each injection, the convulsive behavior was observed for1hour, and resultant seizures were scored as Racine criterion. The10rats in the saline group were injected sodium chloride intraperitoneally by the same dosage as the PTZ group every day. The rats in normal control group were given no treatment. The Racine criterion as follows:stage0, no response; stage1,ear and facial twitching; stage3,myoclonic jerks and rearing; stage4,clonic convulsions with the animal falling on its side; and stage5,repeated severe tonic-clonic convulsions or lethal convulsions. The animals were considered to be kindled after having received10PTZ injections and having reached at least three consecutive stage4or stage5seizures. The generalized seizure was characterized by symmetric forelimb and hind limb tonus, and then hind limb-clonus and flipping activity. One week after the successfully PTZ kindling, the female rats were taken together with the health male mice and caged overnight by2:1, and the female rat were continue treated as before. Vaginal plug’s founding was recorded as gestational day0(GD0), while the birthday as production day0(PD0). After birth, the pups from the PTZ group were changed fed by the mature female rats of normal control group or the saline treated group. At PD21, the male and female pups were divided into different cages to live. And all the pups were tested with Morris water maze to assess the ability of the learning and memory at PD30. The following day, all rats in each group were anesthetized by10%chloral hydrate and the hippocampuses were quickly separated. The expression of JNK、P-JNK protein in hippocampus was detected through the method of Western Blotting.Results:1Results of Orientation navigation test of the Morris Water Maze:Comparisons were made among the mean escape latencies on each day. The results showed there are no significant difference (P>0.05) between normal control group and physiological saline groups in the5days, but there were significant difference (P<0.05) both the normal control group and physiological saline group compared with PTZ group all the five days. In the normal control group and physiological saline group in the way of the comparison results show the first4days compared each other existing statistical significance (P<0.05), and has significant differences (P<0.05) compared with the4th and5th days, however, the4th and5th days comparison shows no statistically significant (P>0.05); The PTZ group was statistical significance (P<0.05) in the first4days, and has significant differences (P<0.05) compared with the4th and5th days, however, the4th and5th days comparison shows no statistically significant (P>0.05); the mean±standard deviation of the escape latency in PTZ group was much longer than that in normal control group and physiological saline group.2Result of Western blotting:The expression of both JNK and p-JNK protein in PTZ group was increased obviously compared to normal control group and saline control group (P<0.05).Conclusions:1From the experiment,we could concluded that the offspring from the mother who had gone through epileptic seizures had been relatively insulted, their cognition is impaired, the learning and memory capacity defected, performance for escape incubation period extended. So, we can see the process of establishing learning and memory relatively slower compared with the NC and SC group.2The ability of learning and memory of the offspring in PTZ group was impaired. The expression level of JNK and P-JNK protein in the hippocampus of the offspring from epilepsy rats were both increased. The study suggested that JNK signaling pathway might play roles in the cognitive impairment that might caused by mother pregnancy periods’seizure insult.