Impact Of Rapamycin On Cognitive Function And Behavior In Rats With Gerontic Malformation Of Cortical Development Induced By X-ray

Objective: This study was to investigate the impact of rapamycin on cognitive impairment and behavior in rats with gerontic malformation of cortical development induced by X-ray.Lay the foundation for the pathogenesis of MCD and the early intervention treatment.Methods:(1)6 health pregnant SD rats at embryonic day 17(E17)were randomly divided into three groups,including normal group,DMSO group(175cGy X-ray irradiated SD rat was treatment by DMSO),and RAP group(175cGy X-ray irradiated SD rat was treatment by rapamycin).All the offspring in each group were fed until 18 month of age,and then as the experimental objects.(2)Behavior observation:Before and after the treatment of rapamycin in SD rats were recorded continuously 24 hour with video surveillance in natural light.Last 3 mouths and drawn 30 days from all the videos(10 hours a day).And analyzed the activity of rats,drinking water,feeding,circadian rhythm,and observed whether spontaneous seizures occurred.(3)Water maze test: Before and after the intervention of rapamycin in SD rats were examined in the Morris water maze placing navigation and spatial probe test for assessing their space learning and memory capability.(4)Took out the rats' brain tissues,observed and photographed the brain tissues gross specimen.And Nissl staining was used to stain frozen section rats brain biopsy tissue.Result:(1)Behavior observation:Elderly rats were less active than young rats in RAP group,spontaneous seizures not occurred in normal health group rats.Rats of MCD(175cGy X-ray irradiated SD rats)were more active than normal group,the main performance is that washing frequently face,licking the hair,fighting,chasing activities.The activity was reduced gradually,moving slow with the increase of age of the rats.(2)Before the drug treatment: All groups of the rats' escape latency was shorten with the increase of the training day,model group rats' escape latency was longer than normal group rats.After the drug treatment: Compared with normal group,RAP group and DMSO group rats' escape latency was longer,but escape latency was shorten with the increase of the training day.Escape latency was no significant differences between RAP group and DMSO group.Escape latency was no significant differences in all groups before and after the drug treatment.Probe trial test: Rats of RAP group and DMSO group before the drug treatment spent significantly less time in the target quadrant and the times across platform than normal group,but there was no significant differences in percentage of target quadrant distance.Rats of RAP group and DMSO group after the drug treatment spent less time in the target quadrant,the percentage of target quadrant distance and the times across platform than normal group,the difference,however,was no statistically significant.(3)Brain pathologic analysis: Brain tissues in DMSO group and RAP group rats were smaller than normal group,especially brain hemisphere.There was no difference between DMSO group and RAP group.Compared with normal group,corpora quadrigemina exposing,corpus callosum partially or completely missing,cerebral cortex thinning,brain gray matter boundary is unclear.The ventricular system,including lateral ventricle,the third ventricle,and the fourth ventricle,was enlarged,especially lateral ventricle significant.Multiple white calcified points in the brain tissues,mainly distributed in the white matter.Nissl staining:Compared with normal group,RAP group and DMSO group rats' cerebral cortex thinning,structure disturbance,the disordered arrangement of cell.Nodulars hyperplasia can be observed in the cerebral cortex and subcortex,varied nodules sizes,the disordered arrangement of cell and neuron axons polarity in nodules.The structural abnormalities and interruption of continuity of the hippocampal can be observed in RAP group and DMSO group.Dispersion phenomenon of neurons can be observed in the hippocampal.FCDclassification: Compared with normal group,Nodules of ectopic brain cortex,agenesis of corpus callosum,structural abnormalities of the hippocampal in group RAP group and DMSO group.FCD classification was divided into FCD?-?.Conclusion:(1)The model of SD rats at E17 induced by X-ray can simulate the MCD in human,shows the abnormal of cerebral cortex,the subependymal nodules,abnormal structure of the hippocampal,cognitive impairment and the change of behavior.(2)The gerontic MCD rats induced by X-ray have the characteristics of cognitive decline in early and serious cognitive impairment.(3)RAP has an protective effect on MCD rats model,improve the behavior performance and decrease the epileptic seizures of low level,however,can not improve cognitive impairment and reverse the pathological damage.