帕金森病模型小鼠脑内5-羟色胺转运蛋白和5-羟色胺1A受体的变化

Changes of the serotonin transporter and 5-HT_(1A) receptor in brain of MPTP-induced Parkinson's disease mice models

目的观察帕金森病(PD)模型小鼠脑内5-羟色胺转运蛋白(SERT)和5-羟色胺1A 受体(5-HT_(1A))的变化。方法 8周龄雄性 C57BL/6小鼠,腹腔注射1-甲基4-苯基-1,2,3,6-四氢吡啶(MPTP),建立 PD 模型小鼠,每组各9只。高剂量组(按体重注射80 mg/kg,每2 h 注射20 mg/kg 1次,共4次);低剂量组20 mg/kg 单次注射;同时设生理盐水对照组。第11天用 ^(131)I-2-((2-((二甲基胺基)甲基)苯基)硫)-5-碘苯胺(ADAM)、4-^(131)I-N-2-[1-(2-甲氧基苯基)-1-哌嗪基乙基]-N-2-吡啶基-苯甲酰胺(^(131)I-MPPI)进行小鼠脑内放射自显影、生物学分布实验,测定 SERT 和5-HT_(1A)的相对含量,并用免疫组织化学法测定 SERT 及5-HT_(1A)阳性细胞数。结果与对照组相比,模型鼠脑内 SERT和5-HT_(1A)的含量减少,且 MPTP 用量越高减少得越多。放射自显影结果示高剂量组较对照组 SERT 和5-HT_(1A)含量分别减少67%和75%,脑内分布实验示两者分别减少34%和52%,免疫组织化学测定示分别减少41.3%和46.3%。结论 MPTP 对多巴胺神经元的损伤不是特异性的,在 PD 模型小鼠脑中5-HT 神经系统也受到 MPTP 的毒性损伤,SERT 和5-HT_(1A)的相对含量呈不同程度的下调。

Objective To observe the changes of serotonin transporter （SERT） and serotonin 1A receptor （5-HT1A） in brain of 1-methy-4-phenyl-1, 2, 3, 6-tetrahy-dropyridine （MPTP）-induced Parkinson＇s disease （PD） mice models. Methods Eight-week-old male C57BL/6 mice were used. High dose group （ n = 9 ） received a total dose 80 mg/kg MPTP intraperitoneally （ four injections of 20 mg/kg at 2 h intervals） while low dose group （n=9） was given a single injection of 20 mg/kg, and saline injection was used as control. Ten days after last injection of MPTP or saline （control）, the mice were sacrificed for in vivo autoradiography, immunohistochemistry and biodistribution studies. Results Binding of SERT and 5- HT1A in brain of mice models as determined by ^131I-2-（ （2-（（dimethylamino） methyl） phenyl） thio）-5-iodophenylamine （ ADAM ） and ^131I-4-iodo-N-2-[ 1-（ 2-methoxyphenyl ）-1-piperazinyl ethyl ] -N-2-pridinyl-benzamine （MPPI） respectively was decreased with the increased doses of MPTP. Autoradiography of the brain of mice models showed significant reduction of SERT and 5-HT1A in 80 mg/kg MPTP-treated mice as compared with the control group. Immunohistochemical studies also showed that SERT and 5-HT1A decreasd by 41.3% and 46.3% respectively. Furthermore, biodistribution studies exhibited a 34% reduction in SERT and a 52% in 5-HT1A respectively. Conclusions There is significant decrease of both the SERT and 5HT1A receptor in brain of MPTP-induced PD mice models. The observed down-regnlation in both receptors suggests that MPTP do not specifically injure the dopamine neurons, and it down-regnlate both the dopamine and 5-HT neurons in different magnitude.