The Effect Of Manganese Exposure On Cognitive Function And Plasma BDNF Levels

Objectives: To explore the effect of manganese exposure on cognitivefunction and plasma BDNF levels by epidemiological investigation and vitroexperimentsMethods:1.205male smelters of a manganese smelter in Guangxi were chosen asexposure group, and were separated into three exposure subgroups according tomanganese exposure levels;96male workers of a sugar refinery in the samedistrict were selected as control group. All participants were conducted withbasic information questionnaires; cognitive function were evaluated by Beijingversion of MoCA test; collected the peripheral venous blood to determine theplasma BDNF levels by using ELISA; calculated the CEI based on airbornemanganese concentrations and the working hours in different positions; analyzethe CEI levels and the cognitive function, and also the plasma BDNF levels.2.8-day-old primary cultured hippocampal neurons were randomlyexposed to0,50,100,200,400,800μM MnCl2for24h, morphology of neuronswas observed by inverted phase contrast microscope and living rate of neurons was detected by MTT method, and determined the low, the intermediate and thehigh dose manganese was100,400,800μM respectively; neurons were randomlyseparated into the control, low Mn-exposed, intermediate Mn-exposed, highMn-exposed and the rolipram group, the control neurons were cultured for24honly with medium, the rolipram group was exposed to2.0μM rolipram for1h,and then exposed to400μM MnCl2for24h, neurons of other groups wereexposed to medium with100、400、800μM MnCl2respectively for24h, and thenused Annexin V-FITC apoptosis detection kit to detect the apoptosis rate ofneurons and measured the BDNF protein levels by ELISA.Results:1. This study included96control workers and205exposed workers(including80workers with low Mn exposure level,65workers withintermediate Mn exposure level and60workers with high Mn exposure levelaccording to CEI. The average age of the control, low exposure, intermediateexposure, high exposure group was32.28±8.729,35.12±5.705,39.49±6.18,42.01±6.893years respectively，there was a significant difference betweenthem(P<0.05).2. A total52air samples were collected, and31samples complied withregulations of Mn PC-TWA, the percent of eligibility was60%; the TWA wasrange0.048to0.450mg/m3, The TWA of the first and the third smelting branchwere higher than the national Permissible Concentration–Time WeightedAverage, especially that of the first branch, which was0.450mg/m3.3. The other subtest and total MoCA scores of control workers weredifferent from other exposed workers expect for the language scores; thelanguage scores of low exposed workers（2.10±0.072） were higher thancontrols（2.01±0.066）, but there was no difference. In addition, the results of partial correlation analysis between MoCA scores and Mn-CEI showed that theywere negative relation, and the correlation coefficient of total MoCA scores andMn-CEI was r=-0.310, P﹤0.01.4. There is a positive correlation between total MoCA scores and plasmaBDNF levels, r=0.279, P﹤0.01.5. After controlling the age, education level, marital status and nation,plasma BDNF levels of control workers(26015.71pg/ml) was higher thanother exposed group, and that of low exposure group(17915.69pg/ml) washigher than low exposure group(13115.90pg/ml).6. Results of the multiple linear regression analysis showed that thecognitive function was significantly affected by age, education, Mn exposurelevels and smoking status(P<0.05).7. Manganese can lead to morphology of neurons injury and change, theneurons survival was decreased significantly as Mn exposure levels increased,there was a significant dose-response relationship(r=-0.953， P＜0.01).Compared to400μM MnCl2group, the living rate of400μM MnCl2+10.0μMrolipram group was higher.8. The apoptosis rate of neurons was evaluated with the increasing of Mnexposure levels, there is a significant positive relationship between total cellapoptosis rate and manganese exposure levels (r=0.999, P＜0.01). In earlyapoptosis, apoptosis rate of400μM and800μM MnCl2neurons weresignificantly higher than0μM MnCl2neurons(P＜0.01), and there was nodifference between400μM MnCl2+10.0μM rolipram and400μM MnCl2neurons,and also between the100μM and0μM MnCl2neurons. In late apoptosis, therewas a significant difference between800μM and0μM MnCl2neurons(P＜0.01).In total apoptosis, apoptosis rate of400μM and800μM MnCl2neurons were obviously higher when compared with0μM MnCl2(P＜0.01), and that of400μM MnCl2+10.0μM rolipram group was lower than400μM MnCl2group(P＜0.05).9. The BDNF levels of intermediate and high exposed neurons were lowerthan controls, and also400μM MnCl2+10.0μM rolipram group was higher than400μM MnCl2group, while there was no statistical significance between0μMand400μM MnCl2neurons. The manganese exposure levels and BDNF levelsshowed a negative correlation(r=-0.986, P＜0.05).10. The result of person correlation analysis showed that cell apoptosis ratewas associated with BDNF levels(r=-0.985, P＜0.05).Conclusions:1. Manganese can decrease cognitive function and plasma BDNF levels,MoCA test and plasma BDNF levels may be were potential biomarkers of earlyimpairment of occupational expose to manganese.2. Manganese can injury rat primary cultured hippocampal neurons, lead toimpairment of morphology and cell apoptosis; manganese can reduce the BDNFlevels, rolipram may restore the injury that manganese induced.3., BDNF may play a role on the cognition impairment induced bymanganese exposure.