MOLECULAR BIOLOGICAL INVESTIGATIONS OF STRESS RESPONSE TO NEURONAL INJURY AND DEVELOPMENT OF NEW THERAPEUTIC APPROACH

神经元损伤应激反应的分子生物学研究和新治疗方法的开发

• 批准号: 06671388
• 负责人: KOHMURA Eiji
• 金额: $ 1.41万
• 依托单位: OSAKA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671388/
• 关键词: Neurotrauma; Gene expression; Molecular biology; Neurotrophic factor; 神経細胞; 虚血; 損傷; c-fos; bFGF; GIF

1.Investigations with in vitro modelUsing primary neuronal cultures obtained from rat fetus, we showed that moderate hypoxic stress the neurons tolerant to subsequent severe hypoxia and that bFGF is involved in the mechanism (Neurosci Res, 1995)2.Investigations with in vivo modelGrowth inhibitory factor (GIF) is known to suppress neurite elongation of cultured neurons and expressed constitutively in the matured brain. Following to the facial nerve transection, GIF mRNA reduced 3 days after transection and continued to be suppressed till 5 weeks (Mol Brain Res, 1995). Furthermore, we showed that expression of GIF mRNA correlates to the functional status of the facial nerve using various injury models (Facial Nerve Res, 1994). In contrast, studies with cortical ablation or MCA occlusion model showed that expression of GIF mRNA reduced 1 day after injury but it increased 4 days after injury (J Neurotrauma, 1995, J Cereb Blood Flow Metab, 1995). Local application of bFGF increased the suppression of GIF mRNA at l day after cortical ablation (J Neurotrauma, 1995).

1.利用从大鼠胎儿中获得的原代神经元培养物进行体外模型研究，我们发现中度缺氧应激可使神经元耐受随后的严重缺氧，并且bFGF参与了这一机制（Neurosci Res, 1995）2。已知生长抑制因子（GIF）抑制培养神经元的神经突伸长，并在成熟的大脑中组成性地表达。面神经横断后，GIF mRNA在横断后第3天减少，并持续抑制至第5周（Mol Brain Res, 1995）。此外，我们通过各种损伤模型表明，GIF mRNA的表达与面神经的功能状态相关（facial nerve Res, 1994）。相比之下，皮质消融或MCA闭塞模型的研究表明，损伤后1天GIF mRNA表达减少，但在损伤后4天表达增加（J Neurotrauma, 1995, J Cereb Blood Flow Metab, 1995）。局部应用bFGF可增加皮质消融后1天对GIF mRNA的抑制（J Neurotrauma, 1995）。

项目成果

Yuguchi T.: "Expression of growth inhibitory factor mRNA following cortical injury in rat." J Neurotrauma. 12. 299-306 (1995)

Yuguchi T.：“大鼠皮质损伤后生长抑制因子 mRNA 的表达。”

Sakaguchi T: "Expression of basic fibroblast growth factor receptor messenger RNA ion the periinfarcted brain tissue." Restor Neurol Neurosci. 7. 29-36 (1994)

Sakaguchi T：“梗死周围脑组织中碱性成纤维细胞生长因子受体信使 RNA 离子的表达。”

Yaguchi T: "Changes in growth inhibitory factor mRNA expression compared with those in c-jun mRNA expression following facial nerve transection." Molecular Brain Research. 28. 181-185 (1995)

Yaguchi T：“面神经横断后，生长抑制因子 mRNA 表达与 c-jun mRNA 表达相比的变化。”

Sakaki T.: "Brief exposure to hypoxia induces bFGF mRNA and protein and protects rat cortical neurons from prolonged hypoxic stress" Neuroscience Research. 23. 289-296 (1995)

Sakaki T.：“短暂缺氧会诱导 bFGF mRNA 和蛋白质，并保护大鼠皮质神经元免受长期缺氧应激”神经科学研究。

Yuguchi T: "Messenger RNA and protein expression of basic fibroblast growth factor receptor after cortical ablation." Mol Brain Res. 25. 50-56 (1994)

Yuguchi T：“皮质消融后碱性成纤维细胞生长因子受体的信使 RNA 和蛋白质表达。”