Correlation Between Cognitive Impairment And Differential Expression Of JNK3 In Hippocampus Of PTSD-like Rats

PartⅠ Association analysis between cognitive impairment and differential expression of JNK3 in hippocampus of PTSD-like rats ObjectiveTo investigate the relationship between cognitive impairment and differential expression of c-Jun N-terminal kinase 3(JNK3)in hippocampus of post-traumatic stress disorder(PTSD)-like rats.MethodsForty male and clean Sprague-Dawley rats were randomly divided into 5 groups: Control group,PTSD 1d group,PTSD 3d group,PTSD 7d group,and PTSD 14 d group,8 in each group.The PTSD model of rats in PTSD groups was made by the internationally recognized single prolonged stimulation(SPS)method.Then cognitive and behavioral changes were investigated by rejection-resistance score,open field experiment and Morris water maze test.HE staining was used to observe the morphological changes in hippocampus of rats.Meanwhile,the changes of JNK3 mRNA and protein in hippocampus of rats were detected by real-time quantitative PCR(RT-PCR)and Western blot.Results(1)Compared with the Control group,the rejection-resistance score increased,the number of standing and crossing decreased in the open field experiment,the times of crossing the platform decreased and the incubation period in the Morris water maze was prolonged of rats in the PTSD 7d and 14 groups(P<0.05);(2)The results of HE staining showed that the hippocampal neurons in the PTSD 7d and14 groups were arranged disorderly and have a smaller number compared with the Control group.(3)The results of RT-PCR and Western blot showed that compared with the Control group,the expression of JNK3 mRNA and protein increased in hippocampus of the PTSD 7d and 14 groups(P<0.05).ConclusionsThe cognitive function of PTSD-like rats is impaired,which may be related to the increased expression of JNK3 gene and protein in hippocampus,JNK3 may be involved in the pathological process of cognitive impairment in PTSD-like rats.PartⅡ Effects of venlafaxine on cognitive impairment and expression of JNK3 in hippocampus of PTSD-like ratsObjectiveTo investigate the effects of venlafaxine hydrochloride on cognitive function damage and JNK3 expression in hippocampus of PTSD-like rats.MethodsThirty-two male and clean Sprague-Dawley rats were randomly divided into 4 groups:Control group,PTSD group,Ven group and PC group,8 in each group.SPS was given in PTSD group,Ven group and PC group.On the basis of SPS,the Ven group and the PC group were given venlafaxine hydrochloride in a dosage of 6.61 mg/kg and saline 6.61 mg/kg for14 days respectly within 6 hours after model establishment.Then cognitive and behavioral changes were investigated by rejection-resistance score,open field experiment and Morris water maze test.HE staining was used to observe the morphological changes in hippocampus of rats.Meanwhile,the changes of JNK3 m RNA and protein in hippocampus of rats were detected by real-time quantitative PCR(RT-PCR)and Western blot.Results(1)Compared with the PC group,the rejection-resistance score decreased,the number of standing and crossing increased in the open field experiment,the times of crossing the platform increased and the incubation period in the Morris water maze was prolonged of rats in the Ven group(P<0.05);(2)The results of HE staining showed that compared with the PC group,the hippocampal neurons in the Ven group were arranged neatly,the quantity increased,and the structure tends to be normal;(3)RT-PCR and Western blot showed that compared with PC group,the expression of JNK3 m RNA and protein in hippocampus of rats in Ven group was decreased(P<0.05).(4)There were no significant differences between the PTSD group and the PC group in the above aspects(P>0.05).ConclusionsEarly administration of venlafaxine in PTSD-like rats can effectively improve the performance of cognitive impairment,which may be related to down-regulation of JNK3 gene and protein expression.