Development of factors that prevent secondary neuronal degeneration

预防继发性神经元变性的因素的开发

• 批准号: 11671370
• 负责人: DESAKI Junzo
• 金额: $ 0.96万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671370/
• 关键词: secondary neuronal degeneration; gerbil; hippocampus; prosaposin-related peptide; apoptosis; Bcl-x_L; passive avoidance experiment; 神経細胞の二次変性; 一過性前脳虚血; インターロイキン3; エリスロポエチン; ジンセノサイドRb_1; secondary neuronal degeneration; gerbil; hippocampus; prosaposin-related peptide; apoptosis; Bcl-x_L; passive avoidance experiment; 神経細胞の二次変性; 一過性前脳虚血; インターロイキン3; エリスロポエチン; ジンセノサイドRb_1

The 7-day infusion of a prosaposin-related 18-mer peptide (18-MP) into the lateral ventricle of gerbils starting 2 hours before or just after 3-min forebrain ischemia is known to prevent the occurrence of learning disability and neuronal death in the hippocampal CA1 field. However, it remains to be determined whether or not intracerebroventricular infusion of the 18-MP starting 72 hours after 3-min forebrain ischemia rescues hippocampal CA1 neurons, and the mechanism (s) by which the 18-MP exerts a protective effect on ischemic hippocampal CA1 neurons also remains to be determined. In the first set of the present experiments, gerbils were infused with the 18-MP for 28 days into the lateral ventricle at 72 hours after 3-min forebrain ischemia. 18-MP infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner as revealed by the step-down passive avoidance task. Subsequent light microscopic examinations showed that pyramidal neurons in the CA1 region of the hippocampus were significantly more numerous in gerbils infused with the 18-MP than in those receiving vehicle infusion. In the second set of the present experiments, the 18-MP prevented in vitro neuronal apoptosis or apoptotic neuron death caused by the nitric oxide (NO) donor sodium nitroprusside (SNP) in a concentration-dependent manner. Moreover, the 18-MP (1-10^5 fg/ml) increased the expression of Bcl-x_L, an antiapoptotic Bcl-2 family protein, in cultured neurons. Thus, the present study indicates that the 18-MP prevents secondary neuronal degeneration after ischemia in vivo possibly through an increase in the expression of the antiapoptotic factor, Bcl-x_L.

从前2小时或之后，已经知道，已知7天与达拉蛋白相关的18-MER肽（18-MP）从3分钟前或仅在3分钟前脑缺血开始2小时开始，以防止在海马CA1场中发生学习障碍和神经元死亡。但是，在3分钟前脑缺血72小时开始，脑脑室内注输注是否尚待确定是否可以挽救海马CA1神经元，以及18-MP在该机制中施加对缺血性海马CA1神经元的保护作用的机制，也仍在确定。在本实验的第一组实验中，在3分钟前脑缺血后72小时，将沙鼠注入18-MP，持续28天。 18-MP输注阻止了缺血诱导的学习障碍以剂量依赖性的方式发生，如降低的被动回避任务所揭示的那样。随后的光学显微镜检查表明，在注入18-MP的沙犬中，海马CA1区域中的锥体神经元明显多于接受媒介物输注的锥体神经元。在本实验的第二组实验中，18-MP以浓度依赖性的方式阻止了由一氧化氮（NO）硝基钠（NO）供体硝化钠（SNP）引起的体外神经元细胞凋亡或凋亡神经元死亡。此外，培养的神经元中18-MP（1-10^5 fg/ml）增加了抗凋亡Bcl-2家族蛋白Bcl-X_L的表达。因此，本研究表明18-MP可以通过体内缺血后的次级神经元变性，这可能是通过抗凋亡因子的表达增加BCl-X_L的。