Manganese Exposure Causes Movement Deficit And The Changes Of Protein Profile Of External Globus Pallidus In Sprague Dawley Rats

Objective:The purpose of this study is to investigate the effects of manganese（Mn）exposure on the motor function of adult SD rats,Through preliminary evaluate the toxic mechanism of Mn in adult SD rats,to screen the key molecules involved in Mn-induced motor dysfunction and analyze the potential connections.Methods:1.In this study,2-month-old adult SD rats were selected as experimental models and divided into control group,1mg/ml Mn-treated group and 20mg/ml Mn-treated group.The Mn-treated group was fed with drinking water containing Mncl₂for 3 months,while the control group was fed with ordinary drinking water.2.After 3 months of Mn exposure,behavioral tests such as sunflower eating test,gait analysis and beam walking test were used to analyze the effects of Mn exposure on motor function of SD rats.3.Inductively coupled plasma technology detects the change of Mn concentration in globus pallidus（GP）tissue.4.Using fluorescence differential two-dimensional gel electrophoresis（2D-DIGE）combined with mass spectrometry to analyze the effect of Mn exposure on the proteome of GP tissue in SD rat.Results:1.Effects of Mn exposure on motor behavior of adult SD rats.:sunflower seed eating test showed that the number of sunflower seeds in Mn-treated group was significantly less than that the control group during the observation period,and most of the melon seeds were irregular bite marks after eating.The gait analysis showed that compared with the control group,the 1mg/ml and 20 mg/ml Mn-exposed groups showed significant obviously disordered gait.The results of balance beam test showed that compared with the control group,the two Mn-treated group had more slip number when passing through the beam,and it increased in a dose-dependent manner,and the calculation of the score through the beam also showed the same results.2.The measurement results of Mn concentration showed that the total Mn concentration of GP increased significantly after Mn exposure,and was positively correlated with the concentration.Similarly,the combined Mn concentration in the 20 mg/ml Mn exposure group was significantly higher than the 1 mg/ml Mn exposure group and control group.3.The results of proteomics showed that a total of 27 differential proteins were screened in the GP tissue of the rats in the Mn exposure group and the control group.These differentially expressed proteins are mainly involved in a variety of biological processes such as glycolytic process,amino acid biosynthesis,carbon metabolism,and antibiotic biosynthesis.Among them,the glycolytic process has a strong correlated.The protein-protein interaction（PPI）analysis of these proteins showed that Eno1,PGAM1,and PKM have strong interactions.Conclusions:1.Mn exposure can affect the motor behavior of adult SD rats after 3months,such as impairing the fine motor function,leading to gait disorder and imbalance of balance ability of rats.2.Excessive Mn into the brain caused brain Mn homeostasis imbalance,resulting in a large amount of Mn accumulated in the GP region.3.The changes of motor behavior in rats exposed to Mn involve many biological processes,among which glycolytic process may be an important pathway of Mn neurotoxicity,and glycolysis related proteins Eno1,PGAM1 and PKM may be the key molecules of Mn toxicity.