Experimental Study On The Effect Of SNAREs Expression In Hippocampus On Cognitive Function In Rats With Spontaneous Recurrent Epilepsy

Objective:To explore whether soluble N-ethylmaleimide-sensitive factor attachment protein receptors?SNAREs?complexes are involved in cognitive dysfunction induced by spontaneous recurrent seizures?SRS?.Methods:65 male SD rats,6-8 weeks old,were randomly divided into the control group and the experimental group.An animal model of epilepsy was established by intraperitoneal injection of kainic acid?KA,10mg/kg?.According to whether SRS occurred,part of rats were injected with Valproic acid?VAP,200 mg/kg?intraperitoneally,and the rats in the experimental group were further divided into?KA-SRS?group,?KA+SRS?group and?KA+SRS+VAP?group.Morris water maze and open field test were conducted to evaluate the cognitive function of rats.Ultrastructural changes of hippocampus were observed by electron microscope.Protein and mRNA levels of SNAREs complex were measured by Western-blot and RT-PCR,respectively.Besides,the Ca²⁺concentration in the hippocampus also was detected.Results:?1?After injecting with KA,46 SD rats were survived.15were distributed into?KA-SRS?group,16 rats into?KA+SRS?group and15 rats into?KA+SRS+VAP?group according to the SRS criteria.?2?In Morris water maze test,the escape latency was significantly elongated?p<0.05?and the times to cross platform was obviously deceased in KA+SRS group when compared with the control group and?KA-SRS?group.In open field experiment test,the moving distance and the residence time of the central area were prolonged in the?KA+SRS?group.All these above indexes were significantly improved in the?KA+SRS+VAP?group.?3?Electron microscopy results showed that the cytoplasm of the experimental group was swollen and irregular,especially in the?KA+SRS?group.?4?The Ca₂⁺concentration in the hippocampus of the?KA+SRS?group?174.26±46.82 nmol/L?was markedly increased when compared with the control group?104.37±24.27 nmol/L?and?KA+SRS+VAP?group?138.48±29.75 nmol/L?.?5?The wester-blot and RT-PCR results showed that the SNARE complexes expression in the hippocampus of the?KA+SRS?group were significantly decreased when compared with both control group and?KA+SRS+VAP?group.Conclusion:The decrease of SNAREs expression in hippocampus of rats with Spontaneous recurrent seizures is related to cognitive impairment.