Study Of Lead And High Fat Diet Exposure On Central Nervous System Inflammatory Microenvironment

Objectives To explore the mechanism of inflammatory microenvironment in the central nervous system under lead and high fat diet through choroid plexus regulating immune cells into the central nervous system.The finding will provide a view to find the biomarkers of neurotoxicity following lead and/or high fat diet exposure.Methods 1.Sixty adults C57 BL / 6J male mice were randomly divided into control group,high fat diet group,lead exposure group,lead+high fat diet exposure group.In the control group,mice were fed with the regular diet and mice in the high fat diet group were fed with high fat diet.Mice in the lead exposure group were fed with the regular diet and drinking water with the concentration of 300 mg / L lead acetate.Mice in the lead+high fat diet group were fed with high fat diet and drinking water with the concentration of300 mg / L lead acetate.The exposure time was 12 weeks.2.Neuronal behavior tests were performed by Morris water maze,new object recognition experiment and open field test.3.The content of lead in mouse hippocampus was detected by ICP-MS.4.The levels of T-CHO,TG and the changes of inflammatory factors and BDNF contents were detected by ELISA and kit.5.The changes of Th1 / CD4+,Th2 / CD4+,Th17 / CD4+percentage in spleen and blood were detected by flow cytometry.6.The m RNA expression of VCAM-1 and ICAM-1 in choroid plexus was detected by real-time PCR.Results 1.The weight of mice fed with high fat diet was significantly higher than that of mice with regular diet(P<0.05).2.The latency periods of the high-fat diet group,lead exposure group,lead+high fat diet group were prolonged than that of control group(P<0.05).Compared with the high fat diet group or lead exposure group,the latency period of the lead+high fat diet group was prolonged and the frequencies of standing up was decreased(P<0.05).Compared with the control group,the length of walking on the central area of mice in the high fat diet group,the lead exposure group,the lead+high fat diet group was decreased(P<0.05).3.Mice with high fat diet were showed the increase levels of total cholesterol(T-CHO),triglycerides(P<0.05).4.The lead content in hippocampus of lead exposure group and lead+high fat diet mice was 8.8 folds and 9.6folds higher than that of control group(P<0.05).5.The levels of inflammatory factors IL-17,IL-6,IL-1? and IFN-? in hippocampus of mice in high fat diet or lead exposed mice were higher than those in control group(P<0.05).The levels of IL-17 and IL-1? in the hippocampus of mice in lead+high fat diet group were higher than those in the individual exposure group(P<0.05).Compared with the control group,the content of BDNF in the high fat diet group and lead exposure group was decreased.6.Compared with the control group,the levels of IL-17 in the serum of mice in high fat diet group,lead exposure group,lead+high fat diet group increased,and TGF-?1 content decreased(P<0.05).The levels of IL-17 in serum of mice in lead+high fat diet group were significantly higher than those in high fat diet group or lead exposure group(P<0.05).7.High-fat diet and lead exposure can lead to increased percentage of Th1/CD4+ and Th17/CD4+ in the blood and spleen(P<0.05).The percentage of Th2/CD4+ in blood and spleen of the lead+high fat diet group decreased(P<0.05).Compared with the high-fat diet group and lead exposure group,the percentage of Th1/CD4+ in the blood of the lead+high fat diet group was higher and the percentage of Th2/CD4+ in the blood and spleen was decreased(P<0.05).8.Compared with control group,the m RNA expression of VCAM-1 and ICAM-1 in choroid plexus were higher(P<0.05).The m RNA expression of VCAM-1 in lead+high fat diet group was significantly higher than that in high-fat diet group or lead exposure group(P<0.05).Conclusions Either high fat diet or lead exposure does lead to the cognitive dysfunction,decrease of learning and memory ability.Moreover,lead exposure combined with high fat diet can intensify central nervous system injury,which may be due to dysfunction of inflammatory system of cells,choroid plexus regulating immune surveillance.