Expression changes of 5-hydroxytryptamine and brain-derived neurotrophic factor in rats with chronic manganism / 中华神经科杂志

ABSTRACT

Objective To observe the expression changes of 5-hydroxytryptamine (5-HT),brainderived neurotrophic factor (BDNF) in rats with chronic manganism.Methods Sixty healthy male Sprague-Dawley rats were randomly divided into control group (n =15) and experimental group (n =45).The experimental group was divided into three subgroups:low-dose group (n =15),middle-dose group (n =15),high-dose group (n =15).The rats in control group were given intraperitoneal injection of normal saline while the rats in low-dose group,middle-dose group,high-dose group were given intraperitoneal injection of 5 mg/kg,15 mg/kg and 25 mg/kg manganese chloride tetrahydrate,respectively for 5 days oncea week and lasted for 12 weeks.The depressive behavior changes of rats were observed by sucrose preference test and open field test.The concentrations of manganese in the striatum of rats were detected by inductively coupled plasma-atomic emission spectrometry.The expression of 5-HT in frontal cortex,hippocampus of rats was determined by high performance liquid chromatography.The expression of BDNF in frontal cortex,hippocampus of rats was examined by Western blotting.The expression of BDNF mRNA was detected using real-time fluorescence quantitative polymerase chain reaction.Results The chronic manganese poisoning rats presented depression-like behavior based on the sucrose preference test and open field test,which was more distinct in high-dose rats.As compared with the control group (frontal cortex (459.65 ± 16.81) ng/g,hippocampus (323.92 ± 17.41) ng/g;tissue wet weight),the expressions of 5-HT were significantly decreased in frontal cortex ((423.45 ± 17.19) ng/g,(376.89 ± 18.87) ng/g,(280.17 ± 25.46) ng/g),hippocampus ((265.71 ± 17.89) ng/g,(214.35 ±23.63) ng/g,(172.67 ± 18.24) ng/g) of the experimental group (F =132.68,69.66,both P ＜ 0.05).As compared with the control group (frontal cortex 0.962 ±0.111,hippocampus 0.873 ± 0.101;the expressions of BDNF were significantly decreased in frontal cortex (0.855 ± 0.106,0.649 ± 0.112,0.506 ± 0.121) and hippocampus (0.731 ± 0.092,0.626 ±0.104,0.544 ± 0.113) with the increasing concentration of MnCl2 which showed dose dependence (F =13.26,18.54,both P ＜ 0.05).As compared with the control group (frontal cortex 0.000 87 ± 0.000 07,hippocampus 0.000 82 ± 0.000 09),the expressions of BDNF mRNA were decreased significantly in frontal cortex (0.000 71 ± 0.000 06,0.000 48 ± 0.000 03,0.000 36 ± 0.000 03) and hippocampus (0.000 57 ± 0.000 05,0.000 49 ± 0.000 04,0.000 38 ± 0.000 05) in the treated group with the increasing concentration of manganese (F =18.46,12.76,both P ＜ 0.05).Conclusion Rats with chronic manganese poisoning could present depression-like behavior and the expression of 5-HT and BDNF is decreased in the frontal cortex and hippocampus with the increased accumulation of manganese.