Effects of S100B on the expressions of dopamine receptors and synthesis, metabolism of neurotransmitters dopamine and 5-hydroxytryptamine / 中华神经科杂志

ABSTRACT

Objective To investigate the effects of S100B on the expressions of dopamine receptors and the synthesis,metabolism of neurotransmitters dopamine,5-hydroxytryptamine which are related to the abnormal motor coordination of Parkinson's disease (PD).Methods The hS100B transgenic mice were established.The mice were divided into S100B transgenic group (TG,n =14),S100B knockout group (KG,n =14) and the non-transgenic control group (CG,n =14).The motor coordination ability of mice was measured by the Rota-rod test.The expressions of dopamine D1 receptor (D1DR),dopamine D2 receptor (D2DR),tyrosine hydroxylase (TH) and phosphorylated TH at Ser19,Ser31,Ser40 in brain tissue were detected by reverse transcription polymerase chain reaction and Western blotting.The levels of Tyr,levodopa,dopamine,homovanillic acid,Trp,5-hydroxytryptamine and 5-hydroxyindoleacetic acid in mesencephalon were measured by high performance liquid chromatography with fluorescence detection.Results Compared with CG,the motor coordination ability of mice (s) showed progressive decline in TG (3 months4.60±0.30vs4.25±0.21,q =5.194;6 months4.52±0.31 vs4.07±0.22,q =6.139;9 months4.43 ± 0.25 vs 3.60 ± 0.18,q =13.484;all P ＜ 0.05),the expressions of D2DR mRNA and protein decreased (1.34 ± 0.13 vs 0.48 ± 0.07,q =21.578;1.05 ± 0.15 vs 0.69 ± 0.10,q =8.063,both P＜0.05) and phosphorylated TH at Serl9 and Ser40 increased (0.95 ±0.10 vs 1.14-0.13,q =4.972;0.94 ± 0.12 vs 1.17 ± 0.14,q=5.382,both P＜ 0.05),the levels of levodopa,dopamine and homovanillic acid were elevated (87.04 ± 11.77 vs 115.28 ± 16.80,q =4.764;56.66 ± 9.87 vs 72.96 ± 11.02,q=3.923;26.58 ± 8.11 vs 38.65 ± 6.67,q=3.981,all P＜ 0.05),the leve1 of 5-hydroxytryptamine was reduced (925.50 ± 74.26 vs 637.87 ± 56.76,q =11.084,P ＜ 0.05),the ratios of homovanillic acid/dopamine and 5-hydroxyindoleacetic acid/5-hydroxytryptamine increased (0.45 ± 0.05 vs 0.54±0.08,q =3.325;0.94±0.07 vs 1.42±0.12,q =12.367,both P＜0.05) in the brain of TG at the age of 9 months old.There was no significant difference of detection indexes between KG and CG.Conclusions S100B plays an important role in the development of PD and the brain-specific S100B transgenic mice can be used to investigate the function of S100B gene on the development of PD.