Effects Of Arsenic Exposure In Drinking Water On Neurobehavioral Development In Rats And Its Correlation With Key Molecules Of Hippo Pathway

Objective: To explore the effect of subchronic arsenic exposure on learning and memory ability and motor function in developing rats and its correlation with the expression of key protein in hippocampal signal pathway.Methods: 40 SPF-grade colostrum SD rats(female and male half),according to weight randomly divided into four groups,each group of 10,infected with poison group rats by free drinking water for 12 weeks,control group normal.The motor function of rats was tested by balance beam test,hanging test and toe print test,and the learning and memory ability of rats was tested by Morris water maze test,hydrogenated atomic fluorescent specular method to detect rat urine,serum arsenic content,to photoscope observation Pathological changes in cerebellum neurons and glial cells;using an electroscope to observe the structure of the cerebral cortex cells,the Western Bolt experiment detected the expression levels of hippo signaling pathways MST1,MST2,LATS1,MOB1,SAV1,p-MST1/2,p-LATS1 in rats.Results: in the navigation experiment,from the second day,the escape latency of the rats in the group of 2 and 10 mg/kg arsenic was longer than that of the rats in the group of 0 mg/kg arsenic(P < 0.05);from the third day,the escape latency of the rats in the group of 10 mg/kg arsenic was longer than that of the rats in the group of 1 mg/kg arsenic(P < 0.05);the results of space search showed that the memory ability of the rats in the group of 10 mg/kg arsenic was lower than that of the rats in the group of 0 mg/kg arsenic(P < 0.05)The results of motor ability test showed that the standing time of 2 mg/kg and 10 mg/kg group was shorter than that of the 2 mg/kg and 10 mg/kg group(P < 0.05);the hanging time of forelimb of 10 mg/kg group was shorter than that of 0 mg/kg and 1 mg/kg group(P < 0.05);There were more times of repeated gait in the 2 mg/kg and 10 mg/kg groups than in the 0 mg/kg and 1 mg/kg groups(P < 0.05);there were shorter times of stride length in the 2 mg/kg and 10 mg/kg groups than in the 0 mg/kg and 1 mg/kg groups(P < 0.05);compared with the 0 mg/kg group,the average time of reaching the target level in the 10 mg/kg group increased(P < 0.05);the suspension ability of forelimb and stride length were negatively correlated with the content of arsenic in urine and blood;the time of walking to the target and the repetition of footprints were positively correlated with the content of arsenic in urine;the content of arsenic in blood and urine was positively correlated with the incubation time of the second day,the third day and the fourth day of the navigation experiment,and positively correlated with the first time of reaching the platform in the space search;In pathological observation,necrosis and glial cell hyperplasia of cerebellum in arsenic-exposed rats were observed under light microscope.Under electron microscope,it was found that the organelles in the cerebral cortex neurons of the arsenic-treated group were edema and decreased,and the nuclear morphology was irregular.In the Western bolt experiment,the expression levels of MST1,LATS1,MOB1 and p-LATS1 in the 2 mg/kg and 10 mg/kg groups increased(P < 0.05);the expression levels of MST2,SAV1 and p-MST1/2 in the 10 mg / kg group increased(P < 0.05).Conclusion: the ability of learning and memory and motor ability of the rats in the development stage is damaged by subchronic arsenic exposure.Arsenic may affect the expression of p-MST1/2 through the regulation of MST1/2,the phosphorylated substrate LATS1 protein of p-MST1/2,and activate the expression of scaffolds(MOB1,SAV1),regulate the Hippo signal pathway at the level of molecular protein,and damage the brain of rats.