The study of physiological and pathophysiological functions of glial cells mediated by neuro-immuno interaction

神经免疫相互作用介导的胶质细胞生理和病理生理功能的研究

• 批准号: 10672036
• 负责人: OKUMA Yasunobu
• 金额: $ 0.51万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672036/
• 关键词: cerebral ischemia; neuronal death; hippocampus; apoptosis; glial cells; GDNF; tyrosine hroxylase; チロシン水酸化酵素; 神経栄養因子

To investigate a possible physiological and pathophysiological functions of glial cells mediated by neuro-immuno interaction, role of glial cell line derived substances on neuronal damage was studied.Glial cell line-derived neurotrophic factor (GDNP) is a potent neurotrophic factor, which has a variety of biological activities that affect several types of neurons in both the central and peripheral nervous systems. In this study, we examined the effects of GDNF on delayed neuronal death in the hippocampal CA1 region of rats after transient forebrain ischemia. Pretreatment with GDNF (1.0 μg), which was directly microinjected into the hippocampal CA1 region, gave significant protection against the delayed hippocampal neuronal death. In addition, pretreatment with GDNF gave significant protection against apoptotic cell death induced by brain ischemia in the hippocampal CA1 region, as determined by in situ staining for DNA fragmentation. These findings suggest that GDNF plays an important r … More ole in delayed neuronal death induced by brain ischemia.In the next series, possible mechanisms of GDNF to protect the delayed neuronal death were studied. It has been shown that dopamine (DA) triggers apoptosis in neuronal cultures and that DA is released in excessive amounts into the hippocampus following transient forebrain ischemia. The expression of tyrosine hydroxylase (TH) mRNA and protein was increased in the hippocampus after transient forebrain ischemia. In contrast, no increase in dopamine β-hydroxylase mRNA and protein in the hippocampus was observed. Interestingly, the induction level of TH mRNA and TH like immunohistochemistry positive terminals in the hippocampus were reduced by intrahippocampal microinjection of GDNF (1.0 μg). In contrast, local GDNF-treatment of normal rats increased the TH mRNA expression. These findings suggest that GDNF protects against neuronal degeneration including delayed neuronal death in the hippocampal CA1 region in part by modulating the expression levels of TH mRNA and protein . Less

为了探讨神经免疫相互作用介导的神经胶质细胞可能的生理和病理生理功能，研究了神经胶质细胞系衍生物质在神经元损伤中的作用。胶质细胞系来源的神经营养因子（GDNP）是一种有效的神经营养因子，具有多种生物活性，影响中枢和周围神经系统中几种类型的神经元。在本研究中，我们检测了GDNF对大鼠短暂性前脑缺血后海马CA1区延迟性神经元死亡的影响。用GDNF （1.0 μg）预处理后直接微注射海马CA1区，对迟发性海马神经元死亡有显著保护作用。此外，通过原位染色检测DNA片段，GDNF预处理对海马CA1区脑缺血诱导的凋亡细胞死亡具有显著的保护作用。提示GDNF在脑缺血引起的延迟性神经元死亡中起重要作用。在接下来的系列中，研究了GDNF保护延迟性神经元死亡的可能机制。研究表明，多巴胺（DA）在神经元培养中触发细胞凋亡，并在短暂的前脑缺血后过量释放到海马中。短暂性前脑缺血后海马组织中酪氨酸羟化酶（TH） mRNA和蛋白表达升高。相比之下，海马多巴胺β-羟化酶mRNA和蛋白未见增加。有趣的是，海马内微量注射GDNF （1.0 μg）可降低海马TH mRNA和TH样免疫组化阳性末梢的诱导水平。与此相反，正常大鼠局部gdnf处理增加了TH mRNA的表达。这些发现表明，GDNF部分通过调节TH mRNA和蛋白的表达水平来防止海马CA1区域的神经元变性，包括延迟的神经元死亡。少

项目成果

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