权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The basic study for the therapy of spinal damages by immuno-related cells and/or immuno suppression drug thorough the production of neurotrophic factors.

利用免疫相关细胞和/或免疫抑制药物通过神经营养因子的产生来治疗脊髓损伤的基础研究。

基本信息

批准号：
12557126
负责人：
NITTA Atsumi
金额：
$ 8.38万
依托单位：
Nagoya University (2002)Gifu Pharmaceutical University (2000-2001)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

FK506, one of the immunosuppressant drugs, has been recently reported to protect neuronal degeneration in the central nervous system, however, the mechanisms of action were not completely clarified. In this study, we investigated the effects of FK506 on the induction of glial cell line-derived neurotrophic factor (GDNF), and involvement of the induced GDNF in the protection against degeneration of dopaminergic neurons. Neurons cultured from embryonic rat hippocampus were cultured in the presence of FK506, and neuronal cell survival and concentration of GDNF in the medium were assessed. GDNF was measured by the specific and sensitive enzyme immunoassay (EIA). In vivo study, FK506 (1.5 mg/kg) was intraperitoneally administrated to mice with or without striatal injection of 6-OHDA. The content of GDNF in the various brain regions, and the degree of neuronal degeneration of striatum were then estimated by the EIA and their rotation behavior induced by methanphetamine, respectively.FK506 elevated GDNF contents in the media conditioned with neurons in dose-dependent manners. FK506 simultaneously protected cultured neurons from the cell death. Further, peripheral administration of FK506 increased GDNF contents in the striatum of mice. The number of rotation induced by metanphetamin was reduced by the administration of FK506 in striatum lesioned mice. The increase of GDNF content and suppression of the number of rotation were well-correlated each other, suggesting protective effects of it on dopaminergic neurons.In Conclusions, 1) FK506 protects dopaminegic degeneration through induction of GDNF in vivo and in virto. 2) Immnonosapressive drugs such as FK506 may be a candidate for a novel therapeutic agent for Parkinson's disease.

FK506是一种免疫抑制药物，最近有报道称其对中枢神经系统的神经元变性具有保护作用，但其作用机制尚不完全清楚。在这项研究中，我们研究了FK506对神经胶质细胞系来源的神经营养因子（GDNF）的诱导作用，以及诱导的GDNF对多巴胺能神经元变性的保护作用。在FK506的存在下培养胚胎大鼠海马神经元，评估培养液中神经元细胞存活率和GDNF浓度。采用特异、灵敏的酶免疫分析法（EIA）测定GDNF。在体内研究中，小鼠腹腔注射FK506 (1.5 mg/kg)，纹状体注射或不注射6-OHDA。然后分别用EIA和甲基苯丙胺诱导的旋转行为来估计大鼠各脑区GDNF的含量和纹状体神经元变性程度。FK506以剂量依赖的方式提高神经元培养基中GDNF的含量。FK506同时保护培养的神经元免于细胞死亡。此外，外周给药FK506可增加小鼠纹状体GDNF含量。在纹状体损伤小鼠中，FK506可减少甲基苯丙胺诱导的旋转次数。GDNF含量的增加与旋转次数的抑制具有良好的相关性，提示其对多巴胺能神经元具有保护作用。结论：1)FK506在体内和体外均通过诱导GDNF保护多巴胺变性。2) FK506等免疫抑制药物可能成为帕金森病的新型治疗药物。