Investigation of sympathetic nerve in Parkinson's disease model mice

帕金森病模型小鼠交感神经的研究

• 批准号: 17591243
• 负责人: FUKUMITSU Nobuyoshi
• 金额: $ 2.11万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591243/
• 关键词: Parkinson's disease; MIBG; norepinephrine; ノルエピネフリン; meta-iodobenzylguanidine(MIBG); 1-metyl-4-phenyl-1,2,3,6-ctetrahydropyridine(MPTP); ノルエピネフリントランスポータ

MPTP was injected to C57BL6 male mice (15 weeks) and Parkinson's disease model mice was made. Injected dose of MPTP was 40 mg/BW. Mice were divided into 6 groups (control, MPTP administration 1-day, 4-days, 7-days, 21-days and 3-times [7, 14, 21 days] before). In RI experiment, (14 mice in each group) 4 hours after ^<125>I-MIBG injection, mice were sacrificed, and cardiac ^<125>I-MIBG uptake, norephephrine, dopamine, thyrosine concentration were measured. In non-RI experiment (20 mice each), striatum dopamine concentration and cardiac norepinephrine transporter was measured. ^<125>I-MIBG uptake was rapidly reduced in 1-day, followed by gradually recovered in 7-day. And it was reduced after 3-times repeated MPTP administration. Striatum dopamine and cardiac norepinephrine concentration showed similar pattern. However, cardiac dopamine and tyrosine concentration showed no significant change, that means norepinephrine synthesis damage is time-dependent. Binding potential of norepinephrine transporter rapidly reduced in 1-day, however no significant change was found after that. In sympathetic nerve of Parkinson's disease model mice, both of binding potential of norepinephrine transporter and norepinephrine synthesis reduced in early stage at first. However, norepinephrine synthesis recovered gradually after that. And long-term and repeated MPTP administration, still more makes reduction of norepinephrine synthesis.

将MPTP注射到C57 BL 6雄性小鼠（15周）中并制备帕金森病模型小鼠。MPTP的注射剂量为40 mg/BW。将小鼠分为6组（对照组、MPTP给药前1天、4天、7天、21天和3次[7、14、21天]）。RI实验中，注射~（14）I-MIBG后4 h<125>处死小鼠，测定心肌<125>~（14）I-MIBG摄取量、去甲肾上腺素、多巴胺、甲状腺素浓度。在非RI实验中（各20只小鼠），测定纹状体多巴胺浓度和心脏去甲肾上腺素转运体。1d<125>内摄取迅速减少，7 d后逐渐恢复。MPTP重复给药3次后，其表达量明显降低。纹状体多巴胺和心脏去甲肾上腺素浓度显示相似的模式。而心脏多巴胺和酪氨酸浓度无明显变化，说明去甲肾上腺素合成损伤具有时间依赖性。去甲肾上腺素转运体的结合电位在第1天迅速降低，但此后无明显变化。在帕金森病模型小鼠交感神经中，去甲肾上腺素转运体结合电位和去甲肾上腺素合成均在早期降低。但此后去甲肾上腺素合成逐渐恢复。而长期反复MPTP给药，更使去甲肾上腺素合成减少。