| Objective Lead is distributed widely in the production and environment.Chronic lead exposure can lead to nerve damage,but the detailed mechanism is unclear.Recent studies have shown that lead exposure can induce copper accumulation in different brain tissues.The role of BCB in maintaining the central nervous system copper homeostasis following lead exposurehas not yet fully elucidated.In current study,the SD rats were exposed to Pb and the levels of copper in hippocampus,cortex,choroid plexus,blood and cerebrospinal fluid after chronic lead exposure and the ability of BCB in clearing copper were detected,as well as copper transporters(CTR1 and ATP7A)and chaperonins(COX17).The fingding will provide new basis for the mechanisms and the important information of new biomakers of lead-induced neurotoxicity.Method Forty five SD male rats were randomly divided into control group,300 ppm and 600 ppm lead exposure group and each group has fifteen rats.The rats took a standard diet,pure water freely.Rats in control group were given 600 ppm sodium acetate and rats in lead group were given 300 ppm or 600 ppm lead acetate respectively for 24 weeks.Morris water maze and open field test were used to detect the neurologic function of rats.The levels of Pb and Cu in blood cerebrospinal fluid cortex hippocampus and choroid plexus were measured by ICP-MS.The detection of the ability of BCB in clearing copper was through a lateral ventricle perfusion test.The expression of CTR1,ATP7 A and COX17 in choroid plexus was observed by laser scanning confocal microscopy so as the level of ROS.Real-time PCR was used to detect the expression level of ctr1,atp7 a and cox17 in choroid plexus.The kits were used to detect the oxidative damage in cortex after lead exposure.Transmission electron microscopy was used to observe the effects of lead exposure on the microstructure of rat choroid plexus epithelial cells.Results 1 The escaping latency of the third and forth days in lead groups were longer than those in control group(P<0.05).The frequencies of crossing the platform in lead groups were decreased when compared with the control group.2 The lateral ventricle perfusion test showed that the Cu64 ratio of isotope activity(in/out)reached plateau at20 min.The ratio of Cu64 in lead group was 0.769±0.026,which was higher than that in control group(0.687±0.018,P<0.05).The ratio of clearance copper in lead group was decreased when compared with the control group(P<0.05).There was no significant difference in terms of C14 ratio of isotope activity(in/out)between lead group and the control group.3 Compared with the control group,the levels of Pb and Cu in blood,cerebrospinal fluid,hippocampus,cortex and choroid plexus were increased in two lead groups(P<0.05).4 Compared with the control group,the AGEs contents in lead groups were increased.The hydroxyl radical inhibition capacity,the activity of GSH-ST and GSH levels in cortex of lead group were lower than those in control group.5 Compared with the control group,the choroid plexus epithelium mitochondria ridges were fused in lead group.Lack of tight junction between cells and some nuclei deformation occurred of choroid plexus of rats in lead group when compared with the control group.6 The fluorescence intensity of CTR1,ATP7 A and COX17 in choroid plexus epithelium was higher than that in the control group after exposure to lead.7 The fluorescence intensity of ROS in choroid plexus epithelium of lead exposure groups were significantly higher than that of control group.8 Compared with the control group,the expression levels of ctr1,atp7 a and cox17 in choroid plexus of lead exposure groups were up-regulated(P<0.05).Conclusion Lead exposure induced copper homeostasis disorder and oxidative damage in central nervous system.The decrease in copper clearance occurred in the blood cerebrospinal fluid barrier,which may be related to the Pb-induced the microstructure damage of the choroid plexus epithelium and the changed expression levels of copper transporters and chaperones. |
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